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A Research Study Comparing How Well Different Doses of the Medicine NNC0519-0130 Can Reduce Kidney Damage in People Living With Chronic Kidney Disease
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06717698
Inclusion Criteria:
* Female of non-childbearing potential, or male.
* For US only: Female of childbearing potential using highly effective non-systemic methods of contraception with low user-dependency at least 2 months prior to screening and willingness to continue using it through-out the study, or male.
* Age 18 years or above at the time of signing the informed consent.
* Diagnosed with type 2 diabetes mellitus greater than or equal to (≥) 180 days before screening, or not diagnosed with type 2 diabetes mellitus.
* HbA1c of 6.5 percentage (%)-10.5 percentage (%) \[48 - 91 millimoles per mole (mmol/mol)\] (both inclusive) if diagnosed with type 2 diabetes mellitus, or HbA1c of less than (\<)6.5 percentage (%) \[\<48 mmol/mol\] if not diagnosed with type 2 diabetes mellitus.
* BMI greater than or equal to (≥) 27.0 kilogram per square metre (kg/m\^2) at screening.
* Kidney impairment defined by serum creatinine and cystatin C-based Egfr greater than or equal to (≥) 15 and less than (\<) 90 mL/min/1.73 m\^2.
* Albuminuria defined by Urine Albumin-to-Creatinine Ratio (UACR) greater than or equal (≥)100 and less than (\<) 5000 milligram per gram (mg/g).
* Treatment with maximum labelled or tolerated dose of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated, in the opinion of the investigator. Treatment dose must be stable for at least 30 days prior to screening.
Exclusion Criteria:
* Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective non-systemic contraception with low user-dependency.
* Lupus nephritis or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
* Receiving immunosuppressive therapy for primary or secondary renal disease within 6 months prior to screening.
* Use of any glucagon-like peptide-1 (GLP-1) RA (including medication with GLP-1 RA activity, e.g., GIP/GLP-1 RA) within 90 days prior to screening.
* Myocardial infarction, stroke, transient ischaemic attack, or hospitalization for unstable angina pectoris within 180 days before screening.
* Chronic or intermittent haemodialysis or peritoneal dialysis within 90 days before screening.
* Only applicable for participants with type 2 diabetes (T2D): Uncontrolled and potentially unstable diabetic retinopathy or diabetic maculopathy. Verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
* Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low-risk prostate cancer, or in-situ carcinomas of the cervix or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN)) within 5 years before screening. DRUG: NNC0519-0130, DRUG: Placebo, DRUG: Semaglutide
Chronic Kidney Disease
Testing the Addition of the Anti-Cancer Drug Tivozanib to Immunotherapy (Pembrolizumab) After Surgery to Remove All Known Sites of Kidney Cancer (STRIKE)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06661720
Inclusion Criteria:
* • Histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features following complete resection of the primary tumor (radical or partial nephrectomy)
* Note: Patients with microscopically positive soft tissue or vascular margins without gross residual disease are permitted
* Intermediate-high risk RCC:
* pT2 grade 4 or sarcomatoid features, N0M0
* pT3 any grade N0, M0
* High-risk RCC
* pT4, any grade, N0, M0
* pT, any stage., any grade, N+, M0
* cM1 no evidence of disease (NED) RCC
* Participants who have had resection of primary tumor (radical or partial nephrectomy) and resection or definitive radiation or ablation of solid, isolated, soft tissue metastases (excluding brain and bone lesions) at the time of primary tumor removal (synchronous) or ≤1 year from primary tumor removal (metachronous)
* Surgery (radical or partial nephrectomy or metastasectomy or ablation) \> 4 weeks but =\< 16 weeks prior to study registration with no ongoing complications from surgery
* No evidence of disease at time of randomization as assessed by investigator by either CT or MRI scan of the brain and chest, abdomen and pelvis
* No prior systemic treatment for RCC
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%)
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 8 g/dL
* Total bilirubin =\< 3 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x upper limit of normal (ULN)
* Calculated (calc.) creatinine clearance \>= 30 mL/min (using Cockcroft Gault equation or the estimated glomerular filtration rate from the modification of diet in renal disease trial)
* Urine protein =\< 1+ on urine analysis (UA) or urine protein creatinine ration (UPCR) \< 2mg/mg
* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test is required =\< 14 days prior to registration
* HIV status: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Hepatitis
* Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with resolved HBV infection, defined as positive hepatitis B core antibody (anti-HBc) and negative hepatitis B surface antigen (HbsAg), are eligible
* Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Cardiac Disease: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class IIB or better
* No history of myocarditis
* No history of clinically significant pneumonitis
* No uncontrolled hypertension (systolic blood pressure \[BP\] \> 150 mm Hg or diastolic BP \> 90 mm Hg) documented on 2 consecutive measurements taken at least 2 hours apart
* No serious non-healing wound, ulcer or bone fracture within 28 days prior to registration
* No serious/active infection requiring parenteral antibiotics
* No moderate or severe hepatic impairment (child-Pugh B or C)
* No significant bleeding disorders within 1 month prior to registration, for example:
* Hematemesis, hematochezia or other gastrointestinal bleeding grade 3 or higher
* Hemoptysis of pulmonary bleeding grade 3 or higher
* Hematuria or other genitourinary bleeding grade 3 or higher
* No history of allogeneic organ transplantation
* No history of allergy of hypersensitivity to study drugs or components
* No condition requiring systemic treatment with either corticosteroid (\> 10 mg daily or prednisone equivalent) within 14 days of treatment initiation or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids and adrenal replacement doses ≤10 mg daily prednisone equivalent are permitted in absence of active autoimmune disease
* No active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other gastrointestinal condition associated with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to registration
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* No patients with a history of autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids \> 10 mg/day, or immunosuppressive drugs) with the following exceptions:
* Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* Brief (\<7 days) use of systemic corticosteroids is allowed when use is considered standard of care
* Patients with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded
* Patients requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded
* Patients with hypothyroidism that is stable with hormone replacement or Sjögren's syndrome will not be excluded • Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment BIOLOGICAL: Pembrolizumab, DRUG: Tivozanib, PROCEDURE: Biospecimen Collection, PROCEDURE: MRI, PROCEDURE: Computed Tomography, PROCEDURE: Biopsy, OTHER: Questionnaire Administration
Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma (RCC), Stage II Renal Pelvis Cancer AJCC v8, Stage III Renal Pelvis Cancer AJCC v8
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC (PSMAddition)
clinicaltrials@northshore.org
MALE
18 years and over
PHASE3
NCT04720157
Inclusion Criteria:
Participants eligible for inclusion in this study must meet all of the following criteria:
• Signed informed consent must be obtained prior to participation in the study
• Patients must be adults ≥18 years of age
• Patients must have an ECOG performance status of 0 to 2
• Patients must have a life expectancy \>9 months as determined by the study investigator
• Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
• Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader
• Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:
• Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR
• Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR
• Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).
• Patients must have adequate organ function: * Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL * Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases * Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
• Albumin ≥2.5 g/dL
• Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial
• Patients must be: Treatment naïve OR minimally treated with: * Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of study therapy or after 45 days whatever happens first. * If received, prior LHRH agonist/antagonist with or without first generation anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued \> 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy. * Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.
Exclusion Criteria:
Participants meeting any of the following criteria are not eligible for inclusion in this study.
• Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
• Any prior systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy (including monoclonal antibodies).
• Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy
• Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed
• Ongoing participation in any other clinical trial
• Use of other investigational drugs within 30 days prior to day of randomization
• Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
• Transfusion for the sole purpose of making a participant eligible for study inclusion
• Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed, baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).
• Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
• Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance).
• Active clinically significant cardiac disease defined as any of the following: * NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF \> 45% with improvement in symptoms to class \< 3. * History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block) * History of familial long QT syndrome or known family history of Torsades de Pointes * Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
• History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
• Any condition that precludes raised arms position
• Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.
• Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
DRUG: 177Lu-PSMA-617, DRUG: 68Ga-PSMA-11, DRUG: ARDT, DRUG: ADT
Prostatic Neoplasms
Lutetium-177 PSMA-617, 177Lu-PSMA-617, Androgen receptor-directed therapy, ARDT, Androgen Deprivation Therapy, ADT, Metastatic Hormone sensitive prostate cancer, mHSPC, Radiographic progression free survival, rPFS, Prostate-specific membrane antigen, PSMA, Gallium-68 PSMA-11, 68Ga-PSMA-11, Radioligand Therapy, RLT
J-Valve Transfemoral Pivotal Study (JOURNEY)
clinicaltrials@northshore.org
ALL
18 years and over
NA
NCT06455787
Inclusion Criteria:
• Symptomatic according to New York Heart Association (NYHA) functional class (FC) II or higher
• Severe AR, defined as follows, as assessed by Imaging Core Laboratory: A. Severe AR by Transthoracic Echocardiography (TTE) (grade 3 or 4) B. OR, if indeterminate AR, by TTE, ANY ONE of the following: i. Cardiac magnetic resonance imaging (CMR)-derived aortic regurgitant fraction (RF) ≥43% ii. CMR-derived RF ≥33% + left ventricular dilation (left ventricular end diastolic volume index \[LVEDVi\]) \>105 mL/m\^2 for men or LVEDVi \>96 mL/m\^2 for women) iii. CMR-derived RF ≥33% + LV ejection fraction (LVEF) ≤55% or left ventricular end systolic volume index (LVESVi) ≥43mL/m\^2; iv. Severe AR by Transesophageal Echocardiography (TEE) (grade 3 or 4)
• High risk for surgery as judged by a multi-disciplinary heart team
• Suitable anatomy to accommodate the insertion, delivery, and deployment of the study devices (see anatomic exclusions below)
• Written informed consent and agreement to comply with all required post-procedure follow-up visits at investigational site.
Exclusion Criteria:
• Previous prosthetic aortic valve (bioprosthesis or mechanical) implant
• Aortic valve stenosis \> moderate\*
• Severe mitral valve or tricuspid valve regurgitation\*
• Severe mitral valve or tricuspid valve stenosis\*
• Active infection, including infective endocarditis
• Cardiac imaging evidence of cardiac mass, thrombus or vegetation
• Inability to tolerate or a condition precluding treatment with antithrombotic (antiplatelet, anticoagulant) therapy
• Renal insufficiency (eGFR \<30 mL/min/1.73m\^2) or end stage renal disease requiring chronic dialysis
• Liver disease (cirrhosis of the liver \[Child-Pugh Class B or C\])
• Blood dyscrasias as defined: leukopenia (WBC \<3000 cells/mcL), thrombocytopenia (platelet count \<50,000 cells/mcL), anemia (hemoglobin \<9 g/dL), history of bleeding diathesis coagulopathy, or hypercoagulable state (unless therapeutically stable)
• Known hypersensitivity or contraindication to aspirin, heparin, bivalirudin, clopidogrel, Nitinol (Nickel, Titanium) or sensitivity to contrast media, which cannot be adequately premedicated
• Left ventricular dysfunction with left ventricular ejection fraction (LVEF) \<25% as measured by resting echocardiogram (or by CMR, when performed)\*
• Clinically significant untreated coronary artery disease requiring revascularization or anticipated coronary revascularization procedure within 12-months post index procedure
• Acute myocardial infarction within 30 days prior to index procedure
• PCI within 30 days prior to index procedure
• Carotid intervention within 6 weeks prior to index procedure or carotid artery disease requiring intervention
• Previous, or planned, other surgical or interventional procedures within 30 days before, during, or within 30 days after the index procedure
• Uncontrolled atrial fibrillation
• Severe right ventricular (RV) dysfunction\*
• Pulmonary hypertension (systolic PA pressure \>70mmHg or systolic PA pressure ≥2/3 of systemic systolic BP)
• Severe chronic obstructive pulmonary disease (COPD) requiring chronic oral steroids or requiring continuous home O2
• Stroke (CVA), transient ischemic attack (TIA) or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 90 days prior to index procedure
• Cardiogenic shock defined as systolic blood pressure \<90 mmHg in addition to signs of tissue hypoperfusion or the need for vasopressors and/or mechanical hemodynamic support to maintain systolic blood pressure ≥90mmHg
• Patient requires mechanical circulatory support within 30 days prior to index procedure
• Estimated life expectancy of less than 24 months due to associated non-cardiac co-morbid conditions
• Pregnancy or intent to become pregnant prior to completion of all protocol follow-up requirements
• Participation in another investigational study that has not reached its primary endpoint
• Considered to be part of a vulnerable population * As assessed by Imaging Core Laboratory Anatomic Exclusions:
• Ascending Aortic diameter \>5 cm\*
• Aortic Annulus Perimeter \<57 mm or \>104 mm\*
• Inappropriate anatomy for femoral introduction and delivery of the study system
• Left ventricular end-diastolic diameter (LVEDD) \>75 mm\*
• Congenital aortic valve disease including Unicuspid, Bicuspid, or Quadricuspid aortic valve anatomy\*
• Congenital univentricle or other condition that, in the opinion of the investigator and/or consulting physician, may constitute an unwarranted surgical risk
• Excessive aortic valve prolapse that would preclude proper seating of the implant in the aortic annulus
• Abdominal/thoracic aortic aneurysm ≥5.0 cm\*
• Aorto-iliac disease requiring intervention to facilitate delivery of access sheath
• Excessive tortuosity of delivery system pathway, defined as severe tortuosity of multiple vessels including iliofemoral, thoracoabdominal aorta, aortic arch, or LV-aortic root angle \>80⁰
• Non-native anatomy in aortic zones 0A \& 0B (aortic valve annulus to the distal margin of the right pulmonary artery); 0C (to innominate) only if deemed unfavorable by the Study Screening Committee * As assessed by Imaging Core Laboratory
DEVICE: J-Valve Transfemoral (TF) System
Aortic Valve Regurgitation, Aortic Valve Disease Mixed
J-Valve Transfemoral System, Transcatheter Therapy, Transcatheter Aortic Valve Replacement, TAVR, Transfemoral
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT03180268
Inclusion Criteria:
* PRIOR TO STEP 1 REGISTRATION:
* The patient must have a newly diagnosed unifocal intracranial meningioma, gross totally resected, and histologically confirmed as WHO grade II based upon pathology findings at the enrolling institution. WHO grade will be assigned according to WHO 2016 criteria
* Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor. GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings. The modified Simpson grade can be inferred from the operative report (surgeon does not need to explicitly describe the Simpson grade for the purposes of eligibility)
* Step 1 registration must occur within 180 days of the initial surgery; this will provide sufficient time for post-operative imaging confirmation of resection extent after resolution of operative changes. Moreover, it will permit additional surgery if needed to achieve a GTR. Within this 180 day interval, a second surgery is permitted in order to achieve GTR, but even with a second surgery, Step 1 registration must occur within 180 days of the initial resection
* GTR must be confirmed on post-operative imaging following the most recent surgery. For protocol enrollment, the assessment of GTR will be made at each site. However, submission of both pre-operative and post-operative MRIs is required for patients. If a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained. All sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration. The post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection. These same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery. Computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
* NOTE: Central pathology review must occur between steps 1 and 2 of registration. Once appropriate pathology specimens are received, central pathology review will occur within 10 business days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
* PRIOR TO STEP 2 REGISTRATION:
* Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central pathology review prior to step 2 registration
* Age \>= 18
* History/physical examination, including neurologic examination within 60 days prior to step 2 registration
* Post-operative Zubrod performance status 0-1 within 60 days prior to step 2 registration
* If the patient is a woman is of childbearing potential, a serum pregnancy test, obtained within 14 days prior to step 2 registration, must be negative, and, if randomized to receive radiation therapy, the woman must agree to use contraception
Exclusion Criteria:
* Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
* Definitive evidence of metastatic meningioma (metastasis, although rare, can occur and is exclusionary)
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix, melanoma in situ, or other non-invasive malignancies are permissible)
* Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
* Major medical illnesses or psychiatric impairments, which in the investigators opinion, will prevent administration or completion of the protocol therapy and/or preclude informed consent; these include, but are not restricted to:
* Unstable angina and/or congestive heart failure requiring hospitalization at the time of step 2 registration
* Transmural myocardial infarction within the last 6 months prior to step 2 registration
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
* Type II neurofibromatosis (NF2)
* Ailments entailing substantial increases in sensitivity and side effect risk from radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human immunodeficiency virus (HIV) with CD4 count \< 200 cells/microliter); HIV testing is not required for eligibility for this protocol, and known HIV positive patients are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \>= 200 cells/microliter within 30 days prior to step 2 registration
* Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction). Note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia PROCEDURE: Biospecimen Collection, OTHER: Clinical Observation, RADIATION: Intensity-Modulated Radiation Therapy, OTHER: Laboratory Biomarker Analysis, PROCEDURE: Magnetic Resonance Imaging, RADIATION: Proton Beam Radiation Therapy, OTHER: Quality-of-Life Assessment
Grade 2 Meningioma, Intracranial Meningioma
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
clinicaltrials@northshore.org
ALL
PHASE2
NCT05564377
Inclusion Criteria:
* Patient must have measurable disease
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 OR patient must have Lansky performance status of \>= 50% or Karnofsky performance status of \>= 50%
* Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as assessed by the enrolling provider
* All patients must have sequencing results available from a National Cancer Institute (NCI) credentialed Designated Laboratory (DL)
* Patients must have locally advanced or advanced histologically documented solid tumors requiring therapy and meet one of the following criteria:
* Patients must have progressed on at least one line of standard systemic therapy OR
* Patients whose disease has no standard treatment that has been shown to prolong overall survival
* Patient must meet one of the following requirements:
* Patients 18 years and older who have tumor amenable to minimal risk image-guided or direct vision biopsy and must be willing and able to undergo a tumor biopsy to obtain samples for research if the patient is to enroll in a ComboMATCH treatment trial OR
* Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
* Tissue must have been collected within 12 months prior to registration to the EAY191 Registration Trial
* Patient must not have had a Response Evaluation Criteria in Solid Tumors (RECIST) response (complete response \[CR\] or partial response \[PR\]) to any intervening therapy after collection of the tissue
* Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available OR
* Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
* Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available
* NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and management instructions. Performance of the mandatory research biopsy or submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection and submission of the blood specimens for the integrated studies will be performed under the consent authority of the specific treatment trial protocol to which the patient is registered. No procedures to collect specimens for research only are to be performed for patients registered to the EAY191 Registration Trial only
* NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial DRUG: Alpelisib, DRUG: Binimetinib, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, DRUG: Fluorouracil, DRUG: Fulvestrant, DRUG: Ipatasertib, DRUG: Leucovorin, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Mutation Carrier Screening, DRUG: Neratinib Maleate, DRUG: Nilotinib Hydrochloride Monohydrate, DRUG: Olaparib, DRUG: Oxaliplatin, DRUG: Paclitaxel, DRUG: Palbociclib, BIOLOGICAL: Panitumumab, PROCEDURE: Positron Emission Tomography, DRUG: Selumetinib Sulfate, DRUG: Sotorasib
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Locally Advanced Malignant Solid Neoplasm, Malignant Female Reproductive System Neoplasm, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Solid Neoplasm, Recurrent Endometrial Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Unresectable HER2-Negative Breast Carcinoma, Unresectable Malignant Solid Neoplasm
Chronic Nausea and Vomiting in Patients With Normal Gastric Emptying Using the Enterra® Therapy System (NAVIGATE) (NAVIGATE)
clinicaltrials@northshore.org
ALL
18 years and over
NA
NCT06464926
Inclusion Criteria:
* Willing and able to complete the informed consent process
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Aged ≥18 years at time of informed consent
* Chronic, drug-refractory nausea that: a) has been present for more than 6 months, and b) has been active within the last 3 months prior to consent
* Patient is able to complete ANMS GCSI-DD surveys on a compatible smart device with: a) a minimum of four (4) ANMS GCSI-DD entries per week for two consecutive weeks, and b) an average ANMS GCSI-DD score for nausea severity of ≥2.5 during the same two-week period
* Refractory or intolerant to two or more of the following antiemetic drug classes: antihistamines, phenothiazines, serotonin type 3 receptor antagonists, dopamine type 2 receptor antagonists, anticholinergics, neurokinin receptor antagonists
* Medically stable, in the opinion of the investigator, during the month prior to consent, with no planned modifications to medical therapy during the course of the study
* Normal gastric emptying as assessed by a qualifying gastric emptying test performed within 2 years of consent if no prior pyloric transection therapy, or within 2 years of consent and after the most recent pyloric transection therapy
* Normal upper endoscopy within 1 year prior to consent (e.g., absence of obstructions, ulcers, or cancers in the esophagus, stomach, or duodenum) performed within 1 year of consent if no prior pyloric transection therapy, or within 1 year of consent and after the most recent pyloric transection therapy
Exclusion Criteria:
* Cognitive impairment or other characteristic that would limit a patient's ability to complete study requirements
* Pyloric transection therapy completed within 1 year of consent
* Documented gastrointestinal (GI) obstruction or pseudo-obstruction
* History of primary swallowing disorders
* History of primary psychogenic vomiting
* History of primary eating disorder
* History of cyclic vomiting syndrome
* History of rumination syndrome
* History of scleroderma
* History of amyloidosis
* History of cannabis hyperemesis syndrome
* Active H. pylori infection
* Evidence of bezoar during most recent endoscopy
* Previous gastric surgery of any type other than a pyloric transection therapy (i.e., pyloroplasty, pyloromyotomy, POP, or G-POEM)
* Uncontrolled thyroid disorder, in the opinion of the investigator
* History of seizures disorders
* Hemoglobin A1c \>8.0%
* Peritoneal dialysis or unstable hemodialysis
* Parenteral or enteral nutritional support
* Active pancreatitis
* History of organ transplant, gross malabsorptive syndromes, celiac disease, or inflammatory bowel disease
* Other GI tract diseases and disorders that the investigator believes may have caused the patient's drug-refractory nausea and/or vomiting
* Malignancy (with the exception of basal cell carcinoma of the skin) currently present, initially diagnosed or recurring within 5 years of consent
* Opioid use
* Current cannabis/cannabinoid use that exceeds: 3 days of usage per week, or 2 occurrences during each day of use, or 3 grams of total usage per week
* Heavy alcohol use, defined as: for men, consuming five or more drinks on any day or 15 or more per week; for women, consuming four or more drinks on any day or 8 or more per week
* Injection of Botox into the pyloric sphincter within 6 months of consent
* Active major levels of anxiety/depression, as determined by the investigator
* History of other clinically significant disease, or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the patient or impact the validity of the study results
* Life expectancy \<1 year
* Pregnant or breastfeeding at the time of consent or intend to become pregnant during the study
* Any underlying disease leading to follow-up by MRI outside of current MR conditional indications
* Glucagon-like peptide 1 (GLP-1) agonist drug use within 6 months of consent
* Participation in other investigational clinical studies
* Existing or prior gastric electrical stimulator implantation DEVICE: Enterra Therapy System
Nausea, Vomiting
Chronic, Nausea, Vomiting, Gastric Electrical Stimulation
De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA) (DEBRA)
clinicaltrials@northshore.org
ALL
50 years to 70 years old
PHASE3
NCT04852887
Inclusion Criteria:
* • The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry/Step 1 and, for patients treated in the U.S., authorization permitting release of personal health information.
* The patient must have an ECOG performance status of 0 or 1.
* The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection.)
* The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
* Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
* The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
* By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm).
* By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible.)
* Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen.
\*\* For patients with a T1a tumor (less than or equal to 0.5 cm in size) or patients at Canadian provinces or approved international sites where Oncotype DX Recurrence Score testing would not be covered, who do not already have an Oncotype DX Recurrence Score at pre-entry/Step 1, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory. Tumor size sample must be greater than or equal to 0.2 cm for analysis.
\*\*\* The Oncotype RS can be run on the biopsy core or surgical specimen. The patient cannot have initiated endocrine therapy prior to tissue collection.
* An Oncotype RS is required for eligibility, however, for a patient whose tumor has already had a MammaPrint test completed as part of usual care when being considered for enrollment and is in the binary "Low" category will meet this eligibility criteria and an Oncotype RS does not need to be performed.
* The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive.
* The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
* Patients may be premenopausal or postmenopausal at the time of pre-entry/Step 1. For study purposes, postmenopausal is defined as:
* Age 56 or older with no spontaneous menses for at least 12 months prior to pre-entry/Step 1; or a documented hysterectomy; or
* Age 55 or younger with no spontaneous menses for at least 12 months prior to pre-entry/Step 1 (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or Documented bilateral oophorectomy.
* The interval between the last surgery for breast cancer (including re-excision of margins) and pre-entry/Step 1 must be no more than 70 days.
* The patient must have recovered from surgery with the incision completely healed and no signs of infection.
* Bilateral mammogram or MRI within 6 months prior to pre-entry/Step 1. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.
Exclusion Criteria:
* • Definitive clinical or radiologic evidence of metastatic disease.
* pT1 mi and pT2 - pT4 tumors including inflammatory breast cancer.
* Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
* Patient had a mastectomy.
* Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
* Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
* Non-epithelial breast malignancies such as sarcoma or lymphoma.
* Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible.)
* Paget's disease of the nipple.
* Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
* Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible.)
* Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re- excision, the patient is eligible.)
* Treatment plan that includes regional nodal irradiation.
* Any treatment with radiation therapy, chemotherapy, or biotherapy, administered for the currently diagnosed breast cancer prior to pre-entry/Step 1.
* History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to pre-entry/Step 1.
* Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention.
\*\* Patients are eligible for BR007 if they receive a short course of preoperative endocrine therapy of less than 6 weeks duration (prior to randomization/Step 2) for this diagnosis after the core biopsy (and can continue postoperatively if:
* the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18, AND
* the patient had not initiated endocrine therapy prior to core biopsy tissue collection.
\*\*\* This does not apply to adjuvant endocrine therapy recommended for this diagnosis which may start any time after surgery including prior to registration (Pre-entry/Step 1).
* Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible. Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.
* Prior breast or thoracic RT for any condition.
* Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
* Pregnancy or lactation at the time of pre-entry/Step 1 or intention to become pregnant during treatment. (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to pre-entry/Step 1.)
* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
* Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
* Use of any investigational product within 30 days prior to pre-entry/Step 1. OTHER: Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane), DRUG: Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)
Stage I Breast Cancer
Safety and Effectiveness of Left Bundle Branch Area Pacing Versus Conventional Cardiac Resynchronization Therapy in Heart Failure (SYNCHRONICITY)
clinicaltrials@northshore.org
ALL
18 years and over
NA
NCT07069738
Inclusion Criteria:
• Patient is age 18 years or above, or of legal age to give informed consent specific to state and national law
• Patient meets a guideline-based indication for a de novo CRT-D device
• Primary prevention indication for ICD therapy
• Ischemic or nonischemic cardiomyopathy with LVEF ≤ 35% within 6 months of enrollment (LVEF must be assessed after the subject has been on GDMT for a minimum of 3 months) using an appropriate method of assessment (i.e. Echo, MRI, etc)
• NYHA class II-IV despite maximally tolerated guideline directed medical therapy (GDMT)\* for at least 3 months \*GDMT is defined as all four drug classes listed below for at least 3 months prior to enrollment unless the investigator provides justification (e.g., contraindicated, not tolerated or cost): Renin Angiotensin System Inhibitors (ACE, ARB, or ARNI) Evidence based betablockers (metoprolol succinate, carvedilol, bisoprolol) Mineralocorticoid antagonists SGLT2 Inhibitor medications
• Sinus rhythm with left bundle branch block (LBBB) defined as a QRS ≥ 140 ms in men and ≥ 130 ms in women with a predominantly negative deflection (QS or rS in lead V1 and mid QRS notching or slurring in at least two of the following leads: 1, aVL, V1, V2, V5, V6) within 3 months of enrollment
• Patient is willing to participate in LATITUDE™ NXT remote patient monitoring
• Patient is willing and capable of providing informed consent and participating in all testing associated with this investigation at an approved study site and at the protocol defined intervals (Note: Use of a legally authorized representative (LAR) is not allowed)
• Patient plans to remain geographically stable (not permanently moving to another location) and can commit to all study participation requirements (procedure, follow-up visits and testing requirements)
Exclusion Criteria:
• Persistent or permanent atrial fibrillation (AF) within 3 months prior to enrollment and documented in the medical record
• Frequent premature ventricular contractions (PVCs), atrial arrhythmias, and/or other causes of expected percentage of cardiac physiologic pacing (CPP) delivery below 95% at the time of enrollment
• Non-LBBB conduction abnormalities (including right bundle branch block (RBB) or intraventricular conduction delay (IVCD)) within 3 months prior to enrollment
• Complete, second degree or high degree atrioventricular (AV) block, that requires pacing at the time of enrollment
• Current or prior pacemaker, ICD or CRT implant (Also includes non-transvenous ICD technology and leadless pacemakers)
• Prior or planned mechanical or bioprosthetic tricuspid valve replacement
• Currently receiving or previously received positive inotrope therapy within 3 months prior to enrollment
• Unstable angina, acute myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention within 3 months prior to enrollment
• History of heart transplantation or left ventricular assist device (LVAD) implantation
• Less than 1 year of life expectancy at the time of enrollment
• Anticipated heart transplantation or LVAD implantation within 1 year of enrollment
• History of ventricular septal defect (VSD)
• Complex congenital heart disease
• Documented diagnosis of cardiac amyloidosis
• Known occlusion or other reason limiting central venous access for transvenous leads
• Women of childbearing potential who are, or plan to become, pregnant during the course of the study (assessment per investigator's discretion)
• Patient currently requiring dialysis
• Patient with known or suspected sensitivity to Dexamethasone Acetate (DXA)
• Patient with contrast dye allergy or unwilling/able to undergo pre-treatment with steroids and/or diphenhydramine
• Inability or refusal to comply with the follow-up schedule including subject living at such a distance from the investigational site that attending follow-up visits would be unusually difficult or burdensome
• Patient is enrolled in any other concurrent study. Co-enrollment into other studies such as observational studies/registries needs prior written approval by BSC. Local mandatory governmental registries are accepted for co-enrollment without approval by BSC.
DEVICE: CRT-D with a Quadripolar LV lead, DEVICE: CRT-D with INGEVITY+ pace/sense lead
Heart Failure - NYHA II - IV
Heart Failure, Conduction System Pacing, Primary Prevention, Cardiac Resynchronization Therapy, Left Bundle Branch Area Pacing
The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation (REACT-AF)
clinicaltrials@northshore.org
ALL
22 years to 85 years old
PHASE3
NCT05836987
Inclusion Criteria:
• 22-85 years of age.
• English speaking participants. Spanish-only speakers may be included in the future at select sites appropriately translated.
• History of non-permanent atrial fibrillation.
• CHA2DS2-VASC score of 1-4 for men and 2-4 for women without prior stroke or Transient Ischemic Attack (TIA), The CHA2DS2-VASc score is a point-based system used to stratify the risk of stroke in Atrial Fibrillation (AF) patients. The acronym CHA2DS2-VASc stands for congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female). Congestive heart failure defined as: The presence of signs and symptoms of either right (elevated central venous pressure, hepatomegaly, dependent edema) or left ventricular failure (exertional dyspnea, cough, fatigue, orthopnea, paroxysmal nocturnal dyspnea, cardiac enlargement, rales, gallop rhythm, pulmonary venous congestion) or both, confirmed by non-invasive or invasive measurements demonstrating objective evidence of cardiac dysfunction and/or ejection fraction \< 40%.
• The participant is on a DOAC at the time of screening and willing to stay on DOAC for duration of study.
• Willing and able to comply with the protocol, including: * Possession of a smart watch-compatible smart phone (iPhone that supports the latest shipping iOS) with a cellular service plan * Be willing to wear the smart watch for the suggested minimum of 14 hours a day * Expected to be within cellular service range at least 80% of the time
• Willing and able to discontinue DOAC
• The participant is willing and able to provide informed consent.
Exclusion Criteria:
• Valvular or permanent atrial fibrillation.
• Current treatment with warfarin and unwilling or unable to take a DOAC.
• The participant is a woman who is pregnant or nursing.
• The participant is being treated with chronic aspirin, another anti-platelet agent, or chronic NSAIDS outside of current medical guidelines (e.g., primary stroke prevention in patients with atrial fibrillation, primary prevention of cardiovascular events, pain relief, fever, gout) and is unwilling or unable to discontinue use for the study duration.
• Existing cardiac rhythm device or indication for a permanent pacemaker, Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) device or planned insertable cardiac monitor. Insertable cardiac monitors are permitted unless they are being used to guide anticoagulation treatment.
• Known or suspected symptomatic or asymptomatic atrial fibrillation lasting ≥ 1 hour/month over the last 3 months.
• Any documented single AF episode lasting ≥ 1 hour on standard of care or study-provided external cardiac monitor of \> 6 days duration performed within 45 days prior to randomization. Shorter monitoring durations may be acceptable for inclusion at the discretion of the site PI based on the totality of monitoring data and approval of the study PI.
• Ablation for AF within the last 2 months.
• Prior or anticipated left atrial appendage occlusion or ligation.
• Mechanical prosthetic valve(s) or severe valve disease.
• Hypertrophic cardiomyopathy.
• Participant needs DOAC for reasons other than preventing stroke or arterial embolism resulting from AF (i.e., preventing Deep Vein Thrombosis (DVT) or PE) or needs permanent OAC (i.e., congenital heart defects, prosthetic heart valve).
• Participants deemed high risk for non-cardioembolic stroke (i.e., significant carotid artery disease defined as stenosis \> 75%) based on the investigator's discretion.
• The participant is enrolled, has participated within the last 30 days, or is planning to participate in a concurrent drug and/or device study during the course of this clinical trial. Co-enrollment in concurrent trials is only allowed with documented pre-approval from the study manager; there is no concern that co-enrollment could confound the results of this trial.
• The participant has a tattoo, birthmark, or surgical scar over the dorsal wrist area on the ipsilateral side that the AFSW may be worn.
• The participant has a tremor on their ipsilateral side that the AFSW may be worn.
• Any concomitant condition that, in the investigator's opinion, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).
• Known hypersensitivity or contraindication to direct oral anticoagulants.
• Documented prior stroke (ischemic or hemorrhagic) or transient ischemic attack.
• Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). AF ablation does not constitute reversible AF.
• \> 5% burden of premature atrial or ventricular depolarizations on pre-enrollment cardiac monitoring.
• History of atrial flutter that has not been treated with ablation (participants in atrial flutter and have been ablated are eligible for enrollment).
• Stage 4 or 5 chronic kidney disease.
• Conditions associated with an increased risk of bleeding: * Major surgery in the previous month * Planned surgery or intervention in the next three months that would require cessation of anticoagulation \> 2 weeks. * History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intra- articular bleeding * Gastrointestinal hemorrhage within the past year unless the cause has been permanently eliminated (e.g., by surgery) * Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days * Hemorrhagic disorder or bleeding diathesis * Need for anticoagulant treatment for disorders other than AF * Uncontrolled hypertension (Systolic Blood Pressure \>180 mmHg and/or Diastolic Blood Pressure \>100 mmHg)
DEVICE: AFSW Guided DOAC, DRUG: Continuous DOAC therapy
Atrial Fibrillation
Atrial Fibrillation, Anticoagulation, AF-sensing Smart Watch, Ischemic Stroke, Systemic Embolism
Evaluation of Treatment Satisfaction and KarXT Utilization Registry (RESKU)
clinicaltrials@northshore.org
ALL
18 years and over
NCT07101094
Inclusion Criteria:
* Aged ≥18 years at index date.
* Have a confirmed diagnosis of schizophrenia before index date.
* Receipt of an initial prescription order for xanomeline and trospium chloride (XT) and plan to fill and initiate such therapy.
* Provide a signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines.
* Agree to use an electronic device to record, or provide paper entry of, patient-reported outcomes (in English or Spanish).
* English or Spanish speaking.
Exclusion Criteria:
* Participation in an interventional study within the last 30 days or plan to participate in such study at the time of eligibility screening.
* Evidence of use of XT prior to time of eligibility screening. DRUG: xanomeline and trospium chloride (X/T) therapy
Schizophrenia
Schizophrenia
Venetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia (AML) (A MyeloMATCH Treatment Trial)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06317649
Inclusion Criteria:
* Patient must be ≥ 60 years of age or adults ˂ 60 who in the opinion of the treating physician are better served by azanucleoside-based therapy rather than intensive, cytarabine-based induction based on clinical status (i.e., performance status), organ dysfunction, or disease biology
* Patient must have a morphologically confirmed diagnosis of AML as determined by the site and confirmed by the treatment verification team, excluding acute promyelocytic leukemia (APL) with PML-RARA, AML with RUNX1-RUNX1T1, or AML with CBFB-MYH11
* Patient must have no prior therapy for AML with the exception of hydroxyurea, all-trans retinoic acid (ATRA), cytarabine-based emergency therapy or leukapheresis to ensure white blood cells (WBC) \< 25,000/mm\^3 prior to starting venetoclax treatment
* Patient must have no prior therapy with hypomethylating agents or FLT3 inhibitors
* Patient must have the FLT3-ITD, D835, or I836del mutation based on MYELOMATCH Protocol
* Patient must be assigned to this protocol by the MYELOMATCH Protocol
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Contraception measures must continue for 30 days after the last dose of venetoclax for all patients who are able to conceive or father children and for 6 months after the last dose of gilteritinib for patients of childbearing potential and for 4 months after the last dose of gilteritinib for male patients with partners of childbearing potential. Patient must not breastfeed during treatment and for 2 months after treatment ends
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Total bilirubin ≤ 2 X institutional upper limit of normal (ULN), unless thought to be elevated due to disease involvement or Gilbert's syndrome, in which case bilirubin ≤ 3 x ULN is allowed (must be obtained ≤ 14 days prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN (must be obtained ≤ 14 days prior to randomization)
* Creatinine clearance ≥ 30 mL/min (must be obtained ≤ 14 days prior to randomization)
* Either measured or estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2021)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* Patients who meet the criteria below must have had an electrocardiogram (ECG) performed with a corrected QT interval using Fridericia's correction (QTcF) interval within normal limits:
* Patient \< 75 years old with a history of cardiac arrythmia, atrial fibrillation, or irregular QTcF interval OR
* Patient \< 75 years old with known genetic predisposition to long QT syndrome OR
* Any patient ≥ 75 years old OR
* Any patient at risk for electrolyte abnormalities, including tumor lysis syndrome
* Normal limits are QTcF ≤ 450 ms for males and QTcF ≤ 460 ms for females. Corrected QT interval method (QTcF) may follow institutional standards
* NOTE: Since older patients and patients with cardiac disease are at risk for prolonged QTcF and many will require supportive care with agents that affect the QTcF, an ECG is recommended if clinically indicated as noted above. If the QTcF is prolonged (\> 450 ms for males and \> 460 ms for females), they should be treated on the Tier Advancement Pathway (TAP) instead of MM1OA-EA02. In patients where ECG is not clinically indicated, QTcF does not need to be documented
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patient must not have the medical necessity for ongoing treatment with a strong CYP3A4 inducing drug
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2 or better
* Patient must not have an uncontrolled infection DRUG: Azacitidine, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Gilteritinib, DRUG: Venetoclax
Acute Myeloid Leukemia
Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (ReMEDy2)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT05065216
Inclusion Criteria:
• Participant is ≥18 years of age.
• Participant weight is 50 kg to 160 kg inclusive.
• Participant to be randomized and treatment initiated within 24 hours of last known normal/AIS stroke onset.
• Participant has NIHSS ≥5 and ≤ 15 at approximately the time of randomization.
• Participant had a pre-morbid mRS score of 0 to 1 (mRS score prior to AIS) as stated by participant or participant's representative.
• Participant and/or legally authorized representative is able to provide informed consent.
• Participant is willing and able to comply with the study protocol, in the Investigator's judgment.
Exclusion Criteria:
• Participant has any evidence of intracranial hemorrhage.
• Participant has received or will receive fibrinolytics for their current AIS.
• Participant has image findings with symptomatic large vessel occlusion at one or more of the following locations: Intracranial carotid I/T/L, M1 or M2 segment MCA, vertebral or basilar artery (BA).
• Participant has large core of established infarction defined as ASPECTS 0-4.
• Participant has or will receive MT for their current AIS.
• Participant has imaging findings and/or symptoms consistent with a posterior circulation stroke.
• Participant has any recorded SBP \< 100 mm HG or MAP \<65 mm Hg; MAP = DBP + \[1/3 (SBP - DBP)\] (measured with noninvasive BP cuff type monitor) after stroke symptom onset and prior to randomization.
• Participant is currently prescribed angiotensin-converting enzyme inhibitor (ACEi) and is unable or unwilling to convert to another antihypertensive pharmacological treatment through Day 29 ±1 day (8 days after last treatment).
• If participant is currently prescribed an ACEi and the last dose of the ACE inhibitor medication is reported to have been taken \< 24 hours before start of IV study drug infusion as stated by participant or participant's representative.
• Participant has a history of clinically significant allergic reactions such as angioedema or anaphylaxis requiring hospitalization.
• Life expectancy estimated at ≤ 1 year prior to enrollment.
• Participant has clinical evidence of an active infection at the time of enrollment requiring parenteral treatment or hospitalization to monitor or manage the infection. NOTE: Treatment of uncomplicated infections with oral antibiotics would not be an exclusion (example treatment of an uncomplicated urinary tract infections or sinus infections with oral antibiotics would not be an exclusion).
• Participant has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency).
• Participant is pregnant or nursing. NOTE: Participants who agree to stop nursing may be considered for inclusion at the discretion of the Investigator.
• Participants of child-bearing potential must agree to use medically acceptable contraceptive measures to prevent pregnancy. All participants of childbearing potential (defined as sexually mature participants who have had menses within the preceding 24 months and have not undergone permanent sterilization methods such as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, etc.) must have a negative serum pregnancy test performed locally at screening. Participants of childbearing potential must agree not to attempt to become pregnant or undergo in vitro fertilization. If participating in sexual activity that could lead to pregnancy, participants must use 2 reliable methods (1 per partner is acceptable) of contraception simultaneously while receiving protocol-specified medication and during the study follow-up period. Participants participating in sexual activity must agree to use, or for their partner to use highly effective birth control methods (those with a failure rate of less than 1% per year when used consistently and correctly) until they have completed the study (after the Day 90 visit). Such methods include: * Combined (estrogen and progesterone containing) hormonal oral, intravaginal, or transdermal contraception associated with the inhibition of ovulation * Progesterone-only oral, injectable, or implantable hormonal contraception associated with the inhibition of ovulation * Intrauterine device (IUD) * Intrauterine hormone-releasing system (IUS) * Bilateral tubal occlusion * Vasectomized partner * Sexual abstinence Participants who are not of reproductive potential (who have been postmenopausal for more than 24 consecutive months or have undergone hysterectomy, bilateral oophorectomy) are not required to use contraception. Participants are prohibited from sperm donation. NOTE: A negative serum pregnancy test will be documented during screening if a participant is of child-bearing potential.
• Participant is currently participating in or has participated in a study using an investigational device or drug or received an investigational drug or investigational use of a licensed drug within 30 days prior to screening.
• Participant does not have sufficient venous access for infusion of study treatment or blood sampling.
• Participant is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-up visits.
• Participant has any other medical condition which in the opinion of the Investigator will make participation medically unsafe or interfere with the study results.
DRUG: Recombinant human tissue kallikrein
Acute Stroke, Ischemic Stroke, Stroke
acute, ischemic, stroke, AIS, tPA, LVO, MT, KLK1, Kallikreins
This is a Study to Learn About How the Combination of the Study Medicines Sigvotatug Vedotin Plus Pembrolizumab Works in People With Non-small Cell Lung Cancer With High Levels of PD-L1. (Be6A Lung-02)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06758401
Inclusion Criteria:
• Participants must meet the following criteria:
• Have pathologically confirmed Stage IIIB or IIIC NSCLC and not be a candidate for surgical resection or definitive chemoradiation, or Stage IV NSCLC per the AJCC Staging Manual (Version 8.0) and the UICC Staging System (Eighth edition).
• Participants with non-squamous histology must have documented negative test results for EGFR, ALK, and ROS1 AGAs and no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies per local standard of care.
• Large cell neuroendocrine carcinoma is excluded.
• Candidate for treatment with pembrolizumab monotherapy per local guidelines.
• Tumor has PD-L1 expression in ≥50% of tumor cells (TPS ≥50%) as determined by local testing
• Measurable disease based on RECIST v1.1 per investigator.
• Resolution of acute effects of any prior therapy to either baseline severity or NCI CTCAE Grade 1 or less (except for AEs not constituting a safety risk in the investigator's judgment), unless otherwise excluded.
Exclusion Criteria:
• Life expectancy of \<3 months in the opinion of the investigator.
• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study.
• Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
• Known or suspected hypersensitivity, intolerance, or contraindication to any excipient contained in the drug formulation of sigvotatug vedotin or pembrolizumab.
• Participants with any of the following respiratory conditions:
• Evidence of noninfectious or drug-induced ILD or pneumonitis
• Known DLCO (adjusted for hemoglobin) \<50% predicted.
• Grade ≥3 pulmonary disease unrelated to underlying malignancy
• Known active CNS lesions are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be eligible. Clinically inactive brain metastases of longest diameter \<0.5 cm are permitted.
• Major surgery (defined as a surgery requiring inpatient hospitalization of at least 48 hours) within 21 days or minor surgery within 7 days prior to first dose of study intervention.
• Receipt of a live vaccine within 30 days prior to first dose of study intervention.
• Pre-existing peripheral neuropathy Grade ≥2 per NCI CTCAE v5.0.
• Uncontrolled diabetes mellitus, defined as HbA1c ≥8.0% or HbA1c between 7.0% and 8.0% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
• Prior immune-related AE that led to anti-PD-(L)1 treatment discontinuation, required a high-dose steroid taper (≥0.5 mg/kg prednisone or equivalent per day) for \>2 weeks, or required treatment with systemic immunosuppressive therapy.
• History of autoimmune disease that has required systemic treatment in the past 2 years
• Participants with prior solid organ or bone marrow transplantation.
• Currently receiving a high-dose steroid (\>10 mg prednisone or equivalent per day) or other immune suppressant or has a condition requiring a chronic high-dose steroid or immune suppressant.
• Prior and concomitant therapy:
• Any prior treatment with MMAE-derived drugs or IB6 targeting agents.
• Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC. * (Neo)adjuvant anti-PD-(L)1 is allowed if recurrence or progression occurred ≥9 months after the last dose. * Other (neo)adjuvant or definitive therapy is allowed if recurrence or progression occurred ≥6 months after the last dose.
• Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received.
• Chemotherapy, biologics, and/or other antitumor treatment with immunotherapy not specifically prohibited that is completed less than 4 weeks prior to first dose of study intervention, or 2 weeks for palliative radiotherapy.
• Any prior therapy with an immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor
• History of or current ongoing infection, including participants positive for active HIV, HBV, or HCV.
• Severe uncontrolled cardiac or cerebrovascular condition within the previous 6 months
DRUG: Sigvotatug Vedotin, DRUG: Pembrolizumab
Non-Small Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung, Carcinoma, Non-Small-Cell Lung (NSCLC)
Lung Cancer, Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer
Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06126276
Inclusion Criteria:
* Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N5 based on the presence of an actionable mutation as defined in EAY191
* Patients must have a HER2 amplified solid tumor except breast cancer.
* If IHC is 0 or 1+, patient (pt) is NOT ELIGIBLE regardless of in situ hybridization (ISH)/FISH or next generation sequencing (NGS) status
* If IHC is 3+, pt IS ELIGIBLE regardless of ISH/FISH or NGS status
* If IHC is 2+, ISH/FISH OR NGS must be positive for the patient to be ELIGIBLE. Otherwise, pt is NOT ELIGIBLE
* If IHC is unknown and…
* ISH/FISH is positive, independent of NGS results, the patient IS ELIGIBLE
* ISH/FISH is negative and NGS positive with ≥ 7 copies, the patient IS ELIGIBLE
* Patients must have recurrent or persistent disease
* No known evidence of RB1 loss or deletion including copy number loss or deleterious mutation
* Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191)
* Patients must have measurable disease based on RECIST 1.1. A second measurable lesion outside of the biopsiable lesion is required
* Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression for 3 months or more and patient is not on steroids and is asymptomatic
* No known leptomeningeal disease
* Patients may have received up to 5 prior lines of systemic therapy
* Prior therapy with trastuzumab or pertuzumab, either alone or in combination, antibody drug conjugates (ADC) such as DS8201a or T-DM1 is allowed
* No prior therapy with HER2 targeting tyrosine kinase inhibitors (TKI) such as neratinib or tucatinib
* No prior therapy with CDK4/6 inhibition
* No cancer directed therapy within 3 weeks prior to registration. For oral therapy, the washout can be reduced to greater than or equal to 5 half lives of the drug. No HER2 targeting ADCs within 30 days prior to registration
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 9 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) ≥ 9 g/dl is acceptable)
* Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
* Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional upper limit of normal (ULN)
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* No active infection requiring parenteral antibiotics
* No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
* No current evidence of malabsorption or chronic diarrhea or any other significant gastro-intestinal disease (e.g gastrectomy, ileal bypass, Crohn's disease, gastroparesis), associated with moderate to severe diarrhea (grade 2 or more) or inability to tolerate oral therapy
* No lung disease causing dyspnea at rest
* No interstitial lung disease with ongoing signs and symptoms at the time of registration
* No history of allergic reaction to the study agents, compound of similar chemical or biologic composition of the study agents or any of their excipients PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, DRUG: Neratinib Maleate, DRUG: Palbociclib
Malignant Female Reproductive System Neoplasm, Malignant Solid Neoplasm, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm
Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT02734537
Inclusion Criteria:
* PRE-REGISTRATION (STEP 0)
* Pathologically proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified \[NOS\]) of the head/neck (oral cavity, oropharynx, hypopharynx or larynx); pathologic stage III or IVA (American Joint Committee on Cancer \[AJCC\] 8): T3-T4a, N0-3, M0 or T1-T2, N1-3, M0
* Patient has undergone total resection of the primary tumor with curative intent
* NOTE: Patient is to be pre-registered to screening (Step 0) and tissue submitted to Foundation Medicine as soon as possible after surgery in order to meet the 8 week deadline to register the patient to Step 1 after surgery; full assay minimum turn-around time is 17-24 days
* For oropharynx primary tumors, the patient must have negative human papillomavirus (HPV) status of the tumor as determined by p16 protein expression using immunohistochemistry (IHC)
* Patients with, per the operative and/or pathology report, positive margin(s) (tumor present at the cut or inked edge of the tumor) which is not superceded by an additional margin of tumor-negative tissue, nodal extracapsular extension, and/or gross residual disease after surgery are not eligible
* A paraffin-embedded surgical tumor tissue specimen has been located is available for shipment to Foundation Medicine, Inc. following pre-registration
* NOTE: Complete the EA3132-specific FoundationOne requisition form
* Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer; patients must not have received chemotherapy or investigational therapy within two years of surgical resection of the primary tumor
* Patient must not have had previous irradiation to the head and neck that would result in overlap in radiation fields for the current disease
* Patients with recurrent disease or multiple primaries are ineligible
* RANDOMIZATION (STEP 1)
* NOTE: Patient must meet all eligibility criteria outlined in pre-registration; patient may not be randomized until site has been notified that the central determination of p53 mutation status of the surgical tumor tissue has been completed and site has been notified of assay completion
* Per the operative report, the gross total resection of the primary tumor with curative intent was completed within 8 weeks prior to randomization
* The patient must have the following assessments done =\< 8 weeks prior to randomization:
* Examination by a head and neck surgeon
* Chest x-ray (or chest computed tomography \[CT\] scan or CT/positron emission tomography \[PET\] of the chest or magnetic resonance imaging \[MRI\]) to rule out distant metastatic disease
* Patient has Eastern Cooperative Oncology Group (ECOG) performance status 0-1 within 2 weeks prior to randomization
* Women must not be pregnant or breast-feeding; females of childbearing potential must have a blood or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study and until 60 days from the last study treatment
* Absolute neutrophil count \>= 1,500/mm\^3 within 4 weeks prior to randomization
* Platelets \>= 100,000/mm\^3 within 4 weeks prior to randomization
* Total bilirubin =\< the upper limit of normal (ULN) within 4 weeks prior to randomization
* Calculated creatinine clearance must be \> 60 ml/min using the Cockcroft-Gault formula within 4 weeks prior to randomization
* Patient must not have an intercurrent illness likely to interfere with protocol therapy DRUG: Cisplatin, RADIATION: Intensity-Modulated Radiation Therapy, OTHER: Laboratory Biomarker Analysis
Head and Neck Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant, Lip and Oral Cavity Squamous Cell Carcinoma, p16INK4a Negative Oropharyngeal Squamous Cell Carcinoma, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oral Cavity Verrucous Carcinoma, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVA Hypopharyngeal Carcinoma AJCC v8, Stage IVA Laryngeal Cancer AJCC v8, Stage IVA Lip and Oral Cavity Cancer AJCC v8, Stage IVA Oral Cavity Verrucous Carcinoma, Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8
A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis
clinicaltrials@northshore.org
ALL
21 years and over
PHASE3
NCT06025578
Inclusion Criteria
* Diagnosis of interstitial lung disease (ILD) with features consistent with progressive ILD within 24 months prior to screening, and ≥ 10% extent of fibrosis on screening high-resolution computed tomography (HRCT).
* If on pirfenidone or nintedanib, participants must have been on a stable dose for at least 90 days prior to screening.
* If not currently on pirfenidone or nintedanib, participants must not have received either of these medications within 28 days prior to screening.
* Mycophenolate mofetil (MMF), mycophenolic acid (MA), azathioprine (AZA), and Tacrolimus are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. If not currently on MMF, MA, AZA, or tacrolimus, participants must not have taken these medications within 28 days prior to screening.
* Traditional disease-modifying antirheumatic drug (DMARDs) (eg. Methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine) are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. If not currently on traditional DMARD, participants must not have taken these medications within 28 days prior to screening.
* Biologic DMARDs (eg. TNF blockers and IL-1 inhibitors) and Janus kinase inhibitors (JAK inhibitors eg. tofacitinib, upadacitinib) are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. If not currently on Biologic DMARD or JAK inhibitor, participants must not have taken these medications within 28 days prior to screening.
* Women who are of childbearing potential must have a highly effective form of contraception and must provide a negative urine/serum pregnancy test.
* Men who are sexually active with women of childbearing potential agree to use male barrier contraception.
Exclusion Criteria
* Idiopathic pulmonary fibrosis with usual interstitial pneumonia (UIP) verification at screening.
* History of stroke or transient ischemic attack within 3 months prior to screening.
* Participants who exhibit symptoms of heart failure at rest.
* Participants who have a current malignancy or a previous malignancy in the past 5 years prior to screening, except for those who have a documented history of cured nonmetastatic squamous cell skin carcinoma, basal cell skin carcinoma, or cervical carcinoma in situ.
* Use of systemic corticosteroids equivalent to prednisone \> 15 mg/day is not allowed within 4 weeks prior to screening and during the study.
* Other protocol-defined Inclusion/Exclusion criteria apply.
DRUG: BMS-986278, DRUG: BMS-986278 Placebo
Progressive Pulmonary Fibrosis
BMS-986278, LPA1 antagonist, Pulmonary fibrosis, Interstitial lung disease, Rheumatoid Arthritis, Connective Tissue Disorders, Sarcoidosis, Scleroderma, Fibrosis, Antifibrotic therapy
Testing the Addition of an IDH2 Inhibitor, Enasidenib, to Usual Treatment (Cedazuridine-Decitabine) for Higher-Risk Myelodysplastic Syndrome (MDS) With IDH2 Mutation (A MyeloMATCH Treatment Trial)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06577441
Inclusion Criteria:
* GENERAL MYLEOMATCH REGISTRATION CRITERIA:
* Patients must be registered to the Master Screening and Reassessment Protocol (MYELOMATCH) and assigned to this protocol by the MATCHBox Treatment Verification Team.
* Participants must not have received prior anti-cancer therapy for AML or MDS.
* Note: Hydroxyurea to control the white blood cell count (WBC) is allowed.
* Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility.
* Participants must not be currently receiving any cytarabine-containing therapy other than up to 1 g/m\^2 of cytarabine, which is allowed for urgent cytoreduction. The use of prior hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide is allowed
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients must have a morphologically-confirmed diagnosis of MDS with a Revised International Prognostic Scoring System (IPSS-R) score ≥ 4.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients must have a detectable pathogenic IDH2 mutation based on the National Cancer Institute (NCI) Myeloid Panel.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): No prior treatment with deoxyribonucleic acid (DNA) methyltransferase inhibitors (ASTX727, azacitidine, or decitabine).
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Prior treatment with growth factors (ESA, granulocyte colony-stimulating factor \[g-CSF\], thrombopoietin \[TPO\] agonist) or luspatercept is allowed.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Prior treatment with lenalidomide with a maximum limit of 1 month of exposure is allowed.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients with therapy-related MDS are allowed.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Age ≥ 18 years.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Unless elevated due to Gilbert's syndrome. In patients with Gilbert's syndrome, if the total bilirubin is ≤ 3.0 x ULN, then they are eligible for enrollment.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 3.0 x upper limit of normal (ULN).
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Creatinine clearance ≥ 30 mL/min
* To be calculated using Cockroft Gault formula.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects.
* Therefore, for women of childbearing potential only, a negative pregnancy test done as part of screening lab work prior to registration is required.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patients on the ASTX727 monotherapy arm (Regimen 1) that do not achieve a CR (complete response), CRL (CR with limited count recovery), or CRh (CR with partial count recovery) after completing 6 cycles of study treatment.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): ECOG performance status ≤ 2.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
* Unless elevated due to Gilbert's syndrome. In patients with Gilbert's syndrome if the total bilirubin is ≤ 3.0 x ULN, then they are eligible for enrollment.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): AST (SGOT)/ALT (SGPT) ≤ 3.0 x upper limit of normal (ULN)
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Creatinine clearance ≥ 30 mL/min
* To be calculated using Cockroft Gault formula.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects. PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Decitabine and Cedazuridine, DRUG: Enasidenib
Myelodysplastic Syndrome
Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/GBG 119/NSABP B-63)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT05633654
Key
Inclusion Criteria:
* Age \> 18 years, with residual invasive triple negative breast cancer (TNBC) in the breast or lymph nodes after neoadjuvant therapy and surgery:
* TNBC criteria for the study is defined as estrogen receptor (ER) and progesterone receptor (PR) ≤ 10%, human epidermal growth factor receptor 2 (HER2)-negative per American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines (immunohistochemistry (IHC) and/or in situ hybridization (ISH)).
* Adequate excision and surgical removal of all clinically evident of disease in the breast and/or lymph nodes and have adequately recovered from surgery.
* Submission of both pre-neoadjuvant treatment diagnostic biopsy and resected residual invasive disease tissue.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Individuals must have received appropriate radiotherapy aligned with local/institutional practice and have recovered prior to starting study treatment.
* Adequate organ function.
Key Exclusion Criteria:
* Stage IV (metastatic) breast cancer as well as history of any prior (ipsi- or contralateral) invasive breast cancer.
* Prior treatment with another stimulatory or coinhibitory T-cell receptor agent (eg, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), OX-40, cluster of differentiation 137 (CD137), prior treatment with any HER2-directed agent, prior endocrine therapy for \> 4 weeks or planned concurrent endocrine therapy while receiving on-study treatment.
* Evidence of recurrent disease following preoperative therapy and surgery.
* Prior treatment with topoisomerase 1 inhibitors or antibody-drug conjugates (ADCs) containing a topoisomerase inhibitor.
* Individuals with germline breast cancer gene (BRCA) mutations.
* Myocardial infarction or unstable angina pectoris within 6 months of enrollment or history of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias or Left ventricular ejection fraction (LVEF) of \< 50%
* Active serious infections requiring anti-microbial therapy.
Note: Other protocol defined Inclusion/Exclusion criteria may apply. DRUG: Sacituzumab govitecan-hziy (SG), DRUG: Pembrolizumab, DRUG: Capecitabine
Triple Negative Breast Cancer
AFT-65, GBG 119, NSABP B-63, OptimICE-RD
Testing Shorter Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With High Risk Prostate Cancer
clinicaltrials@northshore.org
MALE
18 years and over
PHASE3
NCT05946213
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of prostate cancer
* High-risk disease defined as having at least one or more of the following:
* cT3a-T3b by digital exam or imaging (American Joint Committee on Cancer \[AJCC\] 8th edition \[Ed.\]) Note: cT4 by imaging or on digital rectal exam is not allowed
* The patient's prostate specific antigen (PSA) value \> 20 ng/mL prior to starting androgen deprivation therapy (ADT) Note: Patients taking a 5-alpha reductase inhibitor (ex finasteride or dutasteride) are eligible The baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors
* Gleason Score of 8-10
* Pelvic node positive by conventional imaging with a short axis of at least 1.0 cm
* Prostate gland volume less than 100 cc prior to initiation of ADT as reported at time of biopsy or by separate measure with ultrasound or other imaging modalities including MRI or CT scan
* No definitive clinical or radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI); Negative prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is an acceptable substitute
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* No prior radical prostatectomy
* No prior ablative or focal therapy to the prostate (including, but not limited to, transrectal or transurethral high-intensity focused ultrasound \[HIFU\], laser ablation, cryotherapy, irreversible electroporation \[IRE\], and vascular-targeted photodynamic therapy)
* Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone releasing hormone \[LHRH\] agonist and oral anti-androgen) is =\< 185 days prior to registration; Please note: PSA prior to the start of any ADT will be used to define disease
* No contraindication to prostate MRI (required for planning of radiotherapy in both arms)
* Patients enrolled in NRG-GU009 must be enrolled in NRG-GU013 prior to radiation therapy treatment planning and start of radiation therapy PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, RADIATION: External Beam Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Stereotactic Body Radiation Therapy
Prostate Adenocarcinoma, Stage III Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8
Real-world Experience of Catheter Ablation for the Treatment of Arrhythmias (REAL Registry)
clinicaltrials@northshore.org
ALL
18 years and over
NCT04088071
REAL AF Cohort
Inclusion Criteria:
* Symptomatic PAF (AF episode terminate spontaneously within 7 days) or PsAF (AF sustained beyond 7 days, but less than 365 days) subjects who, in the opinion of the investigator, are candidates for catheter ablation.
* \>18 years of age.
* Will be treated with Biosense Webster Inc. ablation technologies
* All AF ablations performed with BWI catheters are included. This includes repeat ablations where the index procedure was performed with a non-BWI catheter.
* Able and willing to participate in baseline and follow up evaluations
* Willing and able to provide informed consent, if applicable.
Exclusion Criteria:
* Enrolled in an investigational drug or device clinical trial, or any trial that dictates the treatment plan
* Long-standing persistent AF (AF greater than one year)
* In the opinion of the investigator, any known contraindication to an ablation procedure
CORE VA Cohort
Inclusion Criteria:
* Documented ventricular arrhythmia appropriate for catheter ablation.
* \>18 years of age.
* Will be treated with Biosense Webster Inc. ablation technologies
* Able and willing to participate in baseline and follow up evaluations
* Willing and able to provide informed consent, if applicable.
Exclusion Criteria:
* Enrolled in an investigational drug or device clinical trial, or any trial that dictates the treatment plan.
* In the opinion of the investigator, any known contraindication to an ablation procedure. DEVICE: Catheter ablation
Paroxysmal Atrial Fibrillation, Persistent Atrial Fibrillation, Ventricular Arrhythmia
CORE VA, REAL AF
Vivistim Registry for Paired VNS Therapy (GRASP) (GRASP)
clinicaltrials@northshore.org
ALL
22 years and over
NCT05301140
Inclusion Criteria:
* Patients implanted with the Vivistim System for upper limb deficits associated with an ischemic stroke
Exclusion Criteria:
* Not eligible for surgery DEVICE: Vivistim System
Upper Extremity Problem
Ischemic Stroke, Paired Vagus Nerve Stimulation
A Study of Enzalutamide Plus the Glucocorticoid Receptor Antagonist Relacorilant Versus Placebo for Patients With High-risk Localized Prostate Cancer
clinicaltrials@northshore.org
MALE
18 years and over
PHASE2
NCT05726292
Inclusion Criteria:
• Histologically or cytologically confirmed prostatic adenocarcinoma without primary small cell histology
• Localized disease: * Surgical resectability must be documented prior to enrollment * No evidence of distant metastatic disease on abdominopelvic imaging, bone imaging * Enlarged lymph nodes below the iliac bifurcation (clinical stage N1) is allowed * Either cross-sectional abdominopelvic imaging + technetium bone scan or PSMA PET imaging will be acceptable to rule out distant metastatic disease
• High or very high-risk disease (https://www.nccn.org/professionals/physician\_gls/pdf/prostate.pdf) as defined by having one or more of the following: * Clinical T3a or higher * Histologic Grade Group 4 or 5 * PSA \>20
• Eastern Cooperative Oncology Group performance status ≤ 1 (Appendix A)
• Total serum testosterone 100 ng/dL
• Patients must have normal hepatic function as defined below: * Total bilirubin \<1.5 X the upper limit of normal (note that in subjects with Gilbert's syndrome, if total bilirubin is \>1.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is ≤1.5 X ULN, the subject may be eligible) * AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal * Albumin 3.0 g/dL
• Patients must have normal bone marrow function as defined below: * Platelet count (plt) 100,000 /L * Hemoglobin (Hgb) 10 g/dL * Absolute neutrophil count (ANC) 1500
• Patients must have adequate renal function as defined below: • glomerular filtration rate (GFR) 30 mL/min
• Ability to understand and the willingness to sign a written informed consent document.
• Patients with active diabetes mellitus on glucose lowering medications are eligible provided they agree to and are able to self-monitor daily blood glucose levels due to potential risk of lowering glucose levels on relacorilant.
• Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following: * Condom (barrier method of contraception) AND * One of the following is required:
• Established use of oral, injected or implanted hormonal method of contraception by the female partner;
• Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner;
• Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner;
• Tubal ligation in the female partner;
• Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months.
• 2 Exclusion Criteria
• Therapy with ANY hormonal therapy for prostate cancer (prior 5-alpha-reductase inhibitors for benign prostate disease is allowed but must be discontinued prior to study initiation).
• Inability to swallow capsules or known gastrointestinal malabsorption.
• History of other malignancies, with the exception of: adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 malignancies that are without evidence of disease, or other cancers curatively treated with no evidence of disease for \> 5 years from enrollment.
• Blood pressure that is not controlled despite \> 2 oral agents (SBP \>160 and DBP \>90 documented during the screening period with no subsequent blood pressure readings \>160/100).
• History of seizure disorder or active use of anticonvulsants. Medications used to treat neuropathic pain such as gabapentin or pregabalin are allowed.
• Serious inter-current infections or non-malignant medical illnesses that are uncontrolled.
• Active psychiatric illness/social situations that would limit compliance with protocol requirements.
• New York Heart Association (NYHA) class II, class III, or IV congestive heart failure (any symptomatic heart failure).
• Concurrent therapy with strong inhibitors of Cytochrome P450 3A4 or CYP2C8 due to concerning possible drug-drug interactions.
• Concurrent therapy with strong inducers of Cytochrome P450 3A4 due to concerning possible drug-drug interactions.
• Presence of concurrent medical conditions requiring systemic glucocorticoids for immunosuppression (e.g. autoimmune diseases, organ transplantation) that is active and has required glucocorticoids in the last 6 months.
DRUG: Relacorilant, DRUG: Enzalutamide, OTHER: Placebo (Sugar Pill), OTHER: Androgen Deprivation Therapy, PROCEDURE: Radical Prostatectomy
Prostate Cancer, Prostate Adenocarcinoma
prostate cancer
Testing Osimertinib as a Treatment for Lung Cancers With an EGFR Exon 20 Change
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT03191149
Inclusion Criteria:
* Participants must have a pathologically-confirmed diagnosis of non-small cell lung cancer (NSCLC)
* Participants must have advanced disease - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 7th edition staging criteria
* An EGFR exon 20 insertion mutation must be detected in the tumor tissue. Patients may be enrolled in the study based on an exon 20 insertion EGFR mutation detected by any Clinical Laboratory Improvement Act (CLIA)-certified tissue assay
* NOTE: Testing results are to be submitted via Medidata Rave and the study chair or delegate will review the reports
* Patients must have measurable disease; baseline measurements and ALL sites of disease must be obtained within 4 weeks to registration
* Patients must have previously received at least one line of therapy for their advanced lung cancer; there are no restrictions on the maximum number of prior therapies allowed
* Participants must not have previously received osimertinib
* Participants must have not previously received therapies targeting PDL1, PD1 or CTLA4 within 6 months (180 days) prior to registration
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
* Hemoglobin \>= 9.0 g/L (within 4 weeks before registration)
* Leukocytes/white blood cells \>= 3,000/mcL (within 4 weeks before registration)
* Absolute neutrophil count \>= 1,500/mcL (within 4 weeks before registration)
* Platelets \>= 100,000/mcL (within 4 weeks before registration)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) if no liver metastases or =\< 3 times ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases (within 4 weeks before registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal; for patients with known hepatic metastases AST and/or ALT =\< 5 x ULN (within 4 weeks before registration)
* Creatinine =\< 1.5 x institutional upper limit of normal (within 4 weeks before registration)
* Participants may not have clinically active or symptomatic interstitial lung disease or interstitial pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention), or a history of clinically significant interstitial lung disease or radiation pneumonitis
* Participants may not have had radiation to the lung fields within four weeks (28 days) of starting treatment. For patients receiving palliative radiation to thoracic vertebrae, ribs or other sites where the radiation field includes the lungs, radiation must be completed at least two weeks before starting treatment. For all palliative radiation to all other sites, at least 7 days must have elapsed prior to starting treatment. At least six months (180 days) must have elapsed prior to starting treatment for radiation given with curative intent. Palliative radiotherapy to control symptoms (including gamma knife technique) is permitted. For stereotactic radiosurgery (SRS) to central nervous system (CNS) lesions, osimertinib can be held on the day of radiation only. For palliative radiotherapy (RT) to other sites of disease outside of the thorax osimertinib (osi) should be held for a minimum of 3 days before radiation and 3 days after RT is completed, but the duration of washout can be adjusted at the investigator's discretion with the approval of the study principal investigator (PI). For thoracic radiation, a 7-10 day washout period before the procedure and one week period after procedure before restarting osimertinib is advised to minimize the risk of pneumonitis. All radiotherapy related toxicities should be managed and ideally resolved before restarting osimertinib. Investigators should consider the radiotherapy when assessing causality if there are any localized adverse events (AEs) following the procedure
* Participants may not have clinically symptomatic brain metastases, leptomeningeal disease, or spinal cord compression. Patients may be on a stable dose of corticosteroids to control brain metastases if they have been on a stable dose for two weeks (14 days) prior to study treatment and are clinically asymptomatic
* Patients must have an ECHO or a nuclear study (MUGA or first pass) within 4 weeks (28 days) prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) \< institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be \>= 50% for the patient to be eligible
* Participants may not have any of the following cardiac criteria:
* Mean resting corrected QT interval (QTc) \>= 470 msec obtained from 3 electrocardiograms (ECGs) using the screening clinic ECG machine-derived QTc value
* No history of QT prolongation associated with other medications that required discontinuation of that medication
* Patient must not be receiving any concomitant medications that are known to be associated with Torsades de Pointes
* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block, second degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: serum/plasma potassium \< LLN; serum/plasma magnesium \< LLN; serum/plasma calcium \< LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
* Symptomatic heart failure - New York Heart Association (NYHA) grade II-IV
* Participants may not have a second, clinically active, cancer. Patients with second cancers which have been treated with curative intent and/or are currently inactive are allowed
* Participants may not be receiving any other investigational agents. Patients previously treated with investigational agents must complete a washout period of at least two weeks or five half-lives, whichever is longer, before starting treatment
* Participants may not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients must have no history of hypersensitivity active or inactive excipients of osimertinib (AZD9291) or drugs with a similar chemical structure or class to osimertinib (AZD9291)
* Patients must not currently be receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4
* If medically feasible, patients taking regular medication, with the exception of potent inducers of CYP3A4, should be maintained on it throughout the study period. Patients taking concomitant medications whose disposition is dependent upon breast cancer resistance protein (BCRP) or P-glycoprotein (Pgp) and which have a narrow therapeutic index should be closely monitored for signs of changed tolerability as a result of increased exposure of the concomitant medication whilst receiving osimertinib (AZD9291)
* NOTE: Use of St John's wort is a contra-indication for osimertinib (AZD9291) use
* If applicable, it is recommended that the starting and maintenance dose of rosuvastatin (due to BCRP inhibition by AZD9291 \[osimertinib\]) should be as low as possible and should be guided by the statin label. Monitoring of low-density lipoprotein (LDL) cholesterol levels is advised. If the subject experiences any potentially relevant adverse events suggestive of muscle toxicity including unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, the statin should be stopped, creatine kinase (CK) levels should be checked, and any appropriate further management should be taken
* Subjects taking warfarin should be monitored regularly for changes in prothrombin time or international normalized ratio (INR)
* No unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2, prior platinum-therapy-related neuropathy
* Patients with refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib (AZD9291) are ineligible
* Women must not be pregnant or breast-feeding because osimertinib (AZD9291) has been shown to cause fetal harm in animal models. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential (WOCBP) and sexually active males must use an accepted and effective method of contraception while receiving protocol treatment or abstain from sexual intercourse for the duration of their participation in the study. WOCBP must use birth control for two weeks prior to the start of the treatment and continue for 6 weeks after the last dose of the study drug. Sexually active male patients must use effective contraception from day 1 of treatment and continue for 4 months after the last dose of the study drug
* Other anticancer agents and investigational agents should not be given while the subject is on study treatment
* Supportive care and other medications that are considered necessary for the subject's wellbeing may be given at the discretion of the investigator
* A guidance regarding potential interactions with concomitant medications is provided PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography with Contrast, PROCEDURE: Echocardiography Test, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, DRUG: Osimertinib
Advanced Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7
Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06203600
Inclusion Criteria:
* Participants must have advanced or locally unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma
* Participants must have PD-L1 CPS (Combined Positive Score) ≥ 1. This test would have been performed as part of standard of care (SOC) pathology testing, using tissue obtained within two years prior to registration and collected prior to or after a frontline regimen
* Participants must have a histologically confirmed diagnosis of microsatellite stable (MSS) and HER2 negative gastric, gastroesophageal junction, or esophageal adenocarcinoma
* Participants must have documented unresectable and/or metastatic disease on CT or MRI imaging completed prior to registration. Imaging must have been completed within 28 days prior to registration for participants with measurable disease. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy. All treatment for brain metastases must have been completed at least 28 days prior to registration
* Participants must have disease progression or intolerance to frontline standard of care (SOC) chemotherapy plus either nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor. Peri-operative chemotherapy plus nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor will count as one line if disease progression occurs while on the therapy or within 6 months of completing the chemotherapy plus nivolumab or pembrolizumab or other PD-1/PD-L1 inhibitor cycle
* Participants must not have received more than one prior line of systemic therapy defined as chemotherapy plus either nivolumab, pembrolizumab, or any other PD-1 or PD-L1 inhibitor, in the stage IV or unresectable setting. Peri-operative or adjuvant nivoluamb or other PD-1/PD-L1 inhibitors would count as one prior line of systemic therapy if patients progressed while on nivolumab (or other PD-1/PD-L1 inhibitors) or within 6 months of stopping it
* Note: Radiation or any other regional therapy options done to address local residual disease or metastatic disease would not count as a line of therapy. Maintenance therapy with a different form of fluoropyrimidine (i.e. switching from capecitabine to fluorouracil \[5FU\]) would not count as another line of therapy
* Participants must not have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as long as there has been a washout period for corticosteroids of ≥ 7 days prior to registration
* Participants must not have prior significant immunotherapy related adverse events requiring permanent discontinuation of the immunotherapy agent including events like pneumonitis, myocarditis, renal failure, Guillain barre syndrome, or myasthenia gravis. Participants with endocrinopathy events leading or not to replacement steroids, thyroid hormone, insulin, or cortisol are eligible
* Participants must not have received a live attenuated vaccination within 28 days prior to registration
* Participants must not have had a major surgery within 28 days or subcutaneous venous access device placement within 7 days prior registration
* Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator. Any participants with postoperative bleeding complications or wound complications from a surgical procedure performed in the last eight weeks should be excluded
* Participants must not have plans to undergo elective or planned major surgery during the clinical trial
* Participants must not have active bleeding or prior history of gastrointestinal (GI) perforation, fistula or significant GI bleeding (requiring transfusion, endoscopic or surgical intervention) within 84 days prior to registration
* Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, investigational agents, biologic or hormonal therapy for cancer treatment while receiving treatment on this study
* Participants must not have a history of a grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy
* Participants must not have a history of grade 3 or 4 immunotherapy related toxicities with the exception of hormonal abnormalities like thyroiditis or thyroid derangements
* Participants must be ≥ 18 years old
* Participants must have Zubrod Performance Status of 0-2
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Leukocytes ≥ 2 x 10\^3/uL (within 28 days prior to registration)
* Absolute neutrophil count ≥ 1.2 x 10\^3/uL (within 28 days prior to registration)
* Hemoglobin ≥ 9.0 g/dL (within 28 days prior to registration)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to registration) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN (within 28 days prior to registration) (unless liver metastases are present, in which case they must be ≤ 5 x ULN)
* Participants must have a calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants' urinary protein must be ≤ 1+ on dipstick or routine urinalysis (UA) within 28 days of registration. Random analysis of urine protein with a normal value is sufficient. If urine dipstick or routine analysis indicated proteinuria ≥ 2+, then a 24-hour urine is to be collected and demonstrate \< 1000 mg of protein in 24 hours to allow participation in the study
* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better
* Participants must have recovered to baseline or \< grade 2 CTCAE version (v) 5.0 from toxicities related to any prior treatments, unless AE(s) are clinically stable on supportive therapy
* Participants must not have experienced arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to registration
* Participants must not have uncontrolled blood pressure within 28 days prior to registration as determined by the treating investigator
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load on the most recent test results obtained within 6 months prior to registration
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must not have a history of inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis). Note: Participants with Graves' disease will be allowed
* Participants must not have a history of pneumonitis that has required oral or IV steroids within the last 12 months prior to registration
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants who can complete patient reported outcomes (FACT-Ga and PRO-CTCAE) questionnaires in English or Spanish must participate in the quality of life studies
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, DRUG: Paclitaxel, OTHER: Questionnaire Administration, BIOLOGICAL: Ramucirumab
Advanced Esophageal Adenocarcinoma, Advanced Gastric Adenocarcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Clinical Stage II Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Esophageal Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Unresectable Esophageal Adenocarcinoma, Unresectable Gastric Adenocarcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma
JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS (Master Record)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06703073
Inclusion Criteria
Each participant must meet all of the following criteria to be enrolled in this study:
* Participant (or their Legally Authorized Representative (LAR)) provides informed consent and agrees to comply with protocol requirements
* Participant is at least 18 years of age or older at the time of consent.
* Participant with signs and symptoms of ARDS according to the Berlin definition of ARDS.
Note that participants on noninvasive ventilation may be screened.
* Participant of childbearing potential must agree to either abstinence or use at least one primary form of contraception, not including hormonal contraception, from the time of screening through Day 28. Additional cohort-specific requirements may apply
* Participant agrees to not participate in another investigational interventional study while participating in this study (i.e., through Day 90).
Exclusion Criteria
Participants will be excluded from the study if any of the following apply:
* Participant with ARDS or at risk of developing ARDS due to the following reasons: trauma, large volume aspiration, or transfusion.
* Participant with pulmonary edema due to cardiogenic pulmonary edema/fluid overload or hypoxemia primarily attributable atelectasis, in the absence of a predisposing risk factor for ARDS.
* Participant who demonstrates an improvement in oxygenation and ventilatory support 24 hours prior to or during screening up to randomization, such that per investigator clinical judgement, the participant is expected to have significant improvement in lung function over subsequent 24 hours regardless of additional interventions.
* Participant is known to be pregnant, nursing, or with a positive (urine and/or serum test) pregnancy test.
* Participant is anticipated to be transferred to another hospital which is not a study site within 72 hours.
* Participant is not expected to survive for 72 hours.
* Participant has been on invasive mechanical ventilation or ECMO for ARDS for more than 48 hours for ARDS at the time of consent.
* Participant has an underlying clinical condition where, in the opinion of the Investigator and based on their clinical judgement, it would be extremely unlikely that the participant would come off ventilation
* Participant has severe COPD requiring continuous long-term home oxygen therapy or mechanical ventilation (noninvasive ventilation or via tracheotomy) except for CPAP or bi-level positive airway pressure used solely for sleep-disordered breathing.
* Participant has interstitial lung disease or idiopathic pulmonary fibrosis requiring continuous chronic home oxygen therapy.
* Participant has NY Heart Association Class IV congestive heart failure.
* Participant has a known allergy to any study medication or any of its excipients.
* Participant is receiving systemic immunosuppressive therapy for solid organ or hematopoietic cancer or transplant anti-rejection medication therapy OR systemic immunosuppressive corticosteroids (prednisone ≥20 mg daily or equivalent). NOTE: Patients onreceiving chronic low dose immunosuppressive therapy may be enrolled(e.g., prednisone \<20 mg/day or equivalent) and patients on stable, long-term maintenance immunosuppression (e.g., tacrolimus, mycophenolate, orsirolimus) and patients receiving physiologic replacement and hormonal therapies for breast cancer (e.g., tamoxifen, letrozole) or prostate cancer (leuprolide, bicalutamide) for \>60 days may be eligible at the investigator's discretion of the investigator in consultation with the medical monitor.
* Participant is receiving ongoing cytotoxic chemotherapy (IV or oral), OR combination targeted/immunotherapy regimens for cancer within the past 60 days. Note: Participants receiving non-myelosuppressive cancer therapy (e.g., hormonal therapy or selected targeted / immunotherapy regimens) may be eligible if therapy has been stable ≥60 days; The use of hydroxyurea to manage patients with chronic myeloid leukemia, polycythemia vera, essential thrombocythemia or sickle cell disease is permitted.
* Participant received treatment with an investigational immunomodulator or immunosuppressant drugs within 5 half-lives or 30 days (whichever is longer) before randomization.
* Participant with concurrent infections or history of the following:
• Known active tuberculosis,
• Known active Hepatitis B, or
• HIV and a CD4 count less than 50 or a detectable viral load of \>200 copies/mL HIV RNA. * Participant received treatment with any other investigational drugs within 30 days prior to consent. * Participant had a history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 28 days of screening or inadequate wound healing secondary to major thoracoabdominal surgery at the time of screening. * Participant is considered by the investigator, for any reason, to be an unsuitable candidate for the study. Participant may have additional cohort-specific requirements.
• Known active tuberculosis,
• Known active Hepatitis B, or
• HIV and a CD4 count less than 50 or a detectable viral load of \>200 copies/mL HIV RNA. * Participant received treatment with any other investigational drugs within 30 days prior to consent. * Participant had a history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 28 days of screening or inadequate wound healing secondary to major thoracoabdominal surgery at the time of screening. * Participant is considered by the investigator, for any reason, to be an unsuitable candidate for the study. Participant may have additional cohort-specific requirements.
DRUG: Cohort A: vilobelimab, DRUG: Cohort A: placebo, DRUG: Cohort B: paridiprubart, DRUG: Cohort B: placebo, DRUG: Cohort C: bevacizumab, DRUG: Cohort C: placebo
Acute Respiratory Distress Syndrome (ARDS), ARDS, ARDS (Acute Respiratory Distress Syndrome), Acute Respiratory Distress Syndrome
BARDA, JUST BREATHE, ARDS, Acute Respiratory Distress Syndrome, Acute Respiratory Failure
JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS- Cohort C: Bevacizumab
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06701656
Inclusion Criteria:
The following inclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT06703073.
* ARDS Severity of mild, moderate or severe, based on PaO2/FiO2 or SpO2/FiO2 assessment at the time of randomization.
Exclusion Criteria:
The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT06703073.
* Participant has a known allergy or hypersensitivity to the active substance/excipients, or Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies
* Participant with established cirrhosis and a modified Child-Pugh Score of 7 or greater
* Participant was dialysis-dependent prior to hospitalization. Participant must have a urine dipstick for proteinuria \< 2+
* The hospitalized participant has a history or currently experiencing the following:
• Participant must not have an international normalized ratio (INR) \>1.5 and/or aPTT \>1.5 × upper limit of normal (ULN) within 7 days prior to initiation of study treatment for participants not receiving anticoagulation. For participants on full dose oral or parenteral anticoagulants for therapeutic purposes the INR and/or activated partial thromboplastin time (aPTT) must be within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the participant on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment.
• Participant with recent serious hemorrhage or history of recent hemoptysis \> 2 episodes (defined as ≥2.5 mL of bright red blood per episode) within 1 month of screening.
• Participant with inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg). Antihypertensive therapy is permitted to achieve these parameters.
• Participant with a history of hypertensive crisis or hypertensive encephalopathy.
• Participant with a history of Grade ≥ 4 venous thromboembolisms.
• Participant with significant vascular disease (eg, aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 3 months of study drug treatment.
• Participant with history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or active gastrointestinal bleeding within 6 months of study drug treatment.
• Participant with serious, non-healing wound, active ulcer, or untreated bone fracture.
• Participant with history or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (ie, in the absence of therapeutic anticoagulation).
• Participant with clinically significant cardiovascular disease including cerebrovascular accident or myocardial infarction within previous 6 months, unstable angina, congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication.
• Participant with a platelet count of \<75×109/L.
• Participant with current or recent (\<10 days prior to initiation of study treatment) use of aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day).
• Participant is receiving a direct anticoagulant (DOAC) such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) without the availability of a reversal agent at the site.
• Participant is receiving a DOAC such as betrixaban (Bevyxxa®) and edoxaban (Lixiana®) for which there is no approved reversal agent.
• Participant has urine dipstick for proteinuria ≥ 2+
DRUG: Cohort C: bevacizumab, DRUG: Cohort C: placebo
Acute Respiratory Distress Syndrome (ARDS), ARDS, ARDS (Acute Respiratory Distress Syndrome), Acute Respiratory Distress Syndrome
BARDA, JUST BREATHE, ARDS, Acute Respiratory Distress Syndrome, Acute Respiratory Failure
JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS- Cohort A: Vilobelimab
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06701682
Inclusion Criteria:
The following inclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT06703073.
* ARDS Severity of moderate or severe based on PaO2/FiO2 or SpO2/FiO2 assessment at the time of randomization
Exclusion Criteria:
The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT06703073.
* Participant with established cirrhosis and a modified Child-Pugh Score of 12 or greater DRUG: Cohort A: vilobelimab, DRUG: Cohort A: placebo
Acute Respiratory Distress Syndrome (ARDS), ARDS, ARDS (Acute Respiratory Distress Syndrome), Acute Respiratory Distress Syndrome
BARDA, JUST BREATHE, ARDS, Acute Respiratory Distress Syndrome, Acute Respiratory Failure
JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS- Cohort B: Paridiprubart
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT06701669
Inclusion Criteria:
The following inclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT06703073:
* ARDS Severity of moderate or severe based on PaO2/FiO2 or SpO2/FiO2 assessment at the time of randomization.
Exclusion Criteria:
The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT06703073.
* Participant has a known allergy or known hypersensitivity to paridiprubart or its excipients, including polysorbate 80
* Participant with established cirrhosis and a modified Child-Pugh Score of 12 or greater DRUG: Cohort B: paridiprubart, DRUG: Cohort B: placebo
Acute Respiratory Distress Syndrome (ARDS), ARDS, ARDS (Acute Respiratory Distress Syndrome), Acute Respiratory Distress Syndrome
BARDA, JUST BREATHE, ARDS, Acute Respiratory Distress Syndrome, Acute Respiratory Failure
IVIG in the Treatment of Autoimmune Small Fiber Neuropathy With TS-HDS, FGFR-3, or Plexin D1 Antibodies
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT04153422
Inclusion Criteria:
• Patients ≥ age 18
• Patient with clinical and biopsy evidence of pure small fiber neuropathy (with or without dysautonomia) as evidenced by reduced IENFD on skin biopsy using PGP 9.5 as the immunostain. Biopsy must have been performed within 12 months of study enrollment. If biopsies were not done at CRL, they will be repeated and done at 3 sites (upper and lower thigh, lower calf), to have consistent and equivalent biopsy data with the follow up biopsy done after 6 mos of treatment
• Patients must have elevated and/or abnormal titers of autoantibodies to TS-HDS-IgM, FGFR3-IgG, or Plexin-D1 measured by the Washington University Neuromuscular Laboratory (St Louis) within 12 mos of enrollment
• Patients must have a baseline pain score on a visual analogue scale (VAS) of Greater or equal to 4/10
• Patients must have a baseline Utah Early Neuropathy Scale (UENS) score of Greater or equal to 4/10
• Small Fiber Neuropathy Screening List (SFNSL) score of 11/84 or greater
• Non-pregnant, non-lactating female. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during treatment
Exclusion Criteria:
• Any other known cause for small fiber neuropathy other than the presence of the elevated titers of TS-HDS-IgM, FGFR3-IgG, or Plexin-D1 autoantibodies
• Patients with generalized, severe musculoskeletal conditions other than SFN that prevent a sufficient assessment of the patient by the physician
• Electromyography/nerve conduction study (EMG/NCS) evidence of large fiber polyneuropathy, to be confirmed by study PI
• Underlying severe heart, kidney, liver disease, or HIV infection, (Note: If there is no previous HIV test result documented within the last 5 years, a test may be performed in order to confirm eligibility)
• Patients with a history of deep vein thrombosis within the last year prior to baseline visit or pulmonary embolism ever; patients with susceptibility to embolism or deep vein thrombosis
• Known significant IgA deficiency with antibodies to IgA
• History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of IVIG 10%
• Known blood hyperviscosity, or other hypercoagulable states
• Use of IgG products within six months prior to enrollment
• Patients with a history of drug or alcohol abuse within the past five years prior to enrollment
• Patients unable to understand or unwilling or unable to comply with the study protocol
DRUG: Panzyga IVIG, DRUG: Placebo
Small Fiber Neuropathy, Autoimmune Small Fiber Neuropathy, Inflammatory Polyneuropathy, Immune-Mediated Neuropathy
Small Fiber Neuropathy, Neuropathy, Intravenous Immunoglobulin, IVIG, TS-HDS antibody, FGFR-3 antibody, FGFR3 antibody, Immune mediated small fiber neuropathy, Panzyga, Plexin D1 antibody