Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery
Anal Melanoma, Bladder Melanoma, Cervical Melanoma
About this trial
This is an interventional treatment trial for Anal Melanoma
Eligibility Criteria
Inclusion Criteria:
- STEP 0 INCLUSION CRITERIA
- Histologically proven mucosal melanoma by local pathology
- Central PD-L1 tumor tissue submission
- STEP 1 INCLUSION CRITERIA
- Receipt of the central PD-L1 testing results available
Disease status-Resected R0 or R1 disease patients. Patients eligible for randomization have resected R0 or R1 disease (with negative margins or positive microscopic margins) that must meet one of the following 4 criteria as defined below:
- Regional lymph node (LN) involvement; OR
- In-transit metastases/satellite primary disease; OR
Single localized, primary disease meeting one of the following site-specific requirements:
- Head/neck - any primary lesion if sinonasal; pT4a or above for nasal or oral cavity, given slightly improved OS
- Anorectal - any primary lesion
- Vaginal/cervical - any primary, as they have 5 year OS rates of 5-25
- Urinary tract - any primary urethral or bladder tumor
- Penile
- Vulvar- AJCC cutaneous stage IIB or higher
- Esophageal/gallbladder - any primary
- Locoregionally recurrent following prior resection, meeting at least one of the above criteria
- In addition, patients must have undergone cross-sectional imaging of the brain, chest, abdomen and pelvis with no evidence of distant metastatic disease
Disease status-Non-resected R2 or metastatic disease patients
- Non-resected R2 or metastatic disease that is assessable and measurable radiographically or by physical examination
Prior Treatment:
- No prior systemic checkpoint inhibitor therapy of mucosal melanoma, including in the adjuvant setting, is allowed. Prior adjuvant chemotherapy or interferon is allowed.
- No other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator.
- Any radiation must have completed 28 days prior to randomization and the patient must have adequately recovered from its effects.
- Surgery must have completed 28 days prior to randomization.
- Surgery must have completed no more than 84 days prior to randomization.
- Not pregnant and not nursing, because this study has an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 50mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Albumin >= 2.8 g/dL
- Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
- Urine protein/creatinine =< 1
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
No cardiovascular disease, including:
- No history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or stenting within 6 months prior to study entry.
- No history of current class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- No refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg despite adequate attempts at anti-hypertensive therapy.
- No history of myocarditis.
- No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, history of Mobitz II second degree or third degree heart block without a permanent pacemaker in Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months.
- No corrected QT interval by Fridericia's formula (QTcF) > 500 msec. Note: if initial QTcF is found to be > 500 ms, two additional EKGs separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard.
No underlying hematologic issues, including:
- Congenital bleeding diathesis
- Gastrointestinal (GI) bleeding requiring intervention within the past 6 months, unless directly related to mucosal melanoma
- Active hemoptysis within 42 days prior to study enrollment.
- Active tumor lesions with cavitations or tumor lesions which invade, encase, or abut major blood vessels. The anatomic location and characteristics of primary tumors or metastases as well as the medical history should be carefully reviewed in the selection of subjects for treatment with cabozantinib/placebo.
- Pulmonary emboli or deep vein thromboses (DVT) that require an active anticoagulation regimen.
- No known or suspected history of cytopenia (low white blood cell [WBC], hemoglobin or platelet count) of greater than 3 months duration with an unknown cause, myelodysplastic syndrome, or hematologic malignancies.
- No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or viral infection requiring treatment at the time of pre-registration (e.g., active symptoms of COVID-19 infection or a post-infectious symptomatic autoimmune syndrome, serious bacterial infections requiring antibiotics).
- No known or suspected gastrointestinal disorder affecting absorption of oral medications.
Comorbid conditions:
- No active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- No history of autoimmune motor neuropathy (e.g., Guillain-Barre syndrome, myasthenia gravis) or non-infectious pneumonitis.
- No history of severe allergic reactions to an unknown allergen or any components of the study drugs or its excipients.
- No history of gastrointestinal perforation or abdominal fistula.
No clinically suspected central nervous system (CNS) (leptomeningeal or parenchymal) metastases. Patients with a history of CNS metastasis(s) will be allowed as long as
- The metastatic site(s) were adequately treated as demonstrated by clinical and radiographic improvement, AND
- The patient has recovered from the intervention (no residual adverse events > Common Terminology Criteria for Adverse Events [CTCAE] grade 1), AND
- The patient has remained without occurrence of new or worsening CNS symptoms for a period of 28 days prior to enrollment.
- No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma) within 2 years.
- No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding due to liver dysfunction.
- No untreated spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression. Spinal metastases must have completed planned radiation or surgical therapy prior to registration.
Concomitant medications:
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study.
- Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
Sites / Locations
- Sutter Auburn Faith Hospital
- Alta Bates Summit Medical Center-Herrick Campus
- Keck Medicine of USC Koreatown
- Los Angeles County-USC Medical Center
- USC / Norris Comprehensive Cancer Center
- Memorial Medical Center
- USC Norris Oncology/Hematology-Newport Beach
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute Palo Alto
- Sutter Roseville Medical Center
- Sutter Medical Center Sacramento
- California Pacific Medical Center-Pacific Campus
- Palo Alto Medical Foundation-Sunnyvale
- UM Sylvester Comprehensive Cancer Center at Aventura
- UM Sylvester Comprehensive Cancer Center at Coral Gables
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- UM Sylvester Comprehensive Cancer Center at Plantation
- Saint Alphonsus Cancer Care Center-Boise
- Saint Alphonsus Cancer Care Center-Caldwell
- Kootenai Health - Coeur d'Alene
- Saint Alphonsus Cancer Care Center-Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Kootenai Cancer Clinic
- Rush - Copley Medical Center
- Northwestern University
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- Carle Physician Group-Mattoon/Charleston
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Carle Cancer Center
- Rush-Copley Healthcare Center
- Mary Greeley Medical Center
- McFarland Clinic - Ames
- McFarland Clinic - Boone
- McFarland Clinic - Trinity Cancer Center
- McFarland Clinic - Jefferson
- McFarland Clinic - Marshalltown
- Bronson Battle Creek
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Ascension Borgess Cancer Center
- Trinity Health Muskegon Hospital
- Cancer and Hematology Centers of Western Michigan - Norton Shores
- Spectrum Health Reed City Hospital
- Marie Yeager Cancer Center
- Munson Medical Center
- University of Michigan Health - West
- Minnesota Oncology - Burnsville
- Mercy Hospital
- Fairview Southdale Hospital
- Abbott-Northwestern Hospital
- Mayo Clinic in Rochester
- Park Nicollet Clinic - Saint Louis Park
- United Hospital
- Parkland Health Center - Farmington
- Missouri Baptist Medical Center
- Sainte Genevieve County Memorial Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Community Hospital of Anaconda
- Billings Clinic Cancer Center
- Bozeman Deaconess Hospital
- Benefis Healthcare- Sletten Cancer Institute
- Kalispell Regional Medical Center
- Community Medical Hospital
- Memorial Sloan Kettering Basking Ridge
- Memorial Sloan Kettering Westchester
- NYU Winthrop Hospital
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Memorial Sloan Kettering Cancer Center
- Case Western Reserve University
- Dayton Physician LLC-Miami Valley Hospital North
- Kettering Medical Center
- Cancer Centers of Southwest Oklahoma Research
- University of Oklahoma Health Sciences Center
- Saint Alphonsus Medical Center-Ontario
- Thomas Jefferson University Hospital
- University of Pittsburgh Cancer Institute (UPCI)
- Asplundh Cancer Pavilion
- Avera Cancer Institute
- M D Anderson Cancer Center
- VCU Massey Cancer Center at Stony Point
- Virginia Commonwealth University/Massey Cancer Center
- HSHS Sacred Heart Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Saint Vincent Hospital Cancer Center at Saint Mary's
- University of Wisconsin Carbone Cancer Center
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Saint Vincent Hospital Cancer Center at Sheboygan
- Saint Vincent Hospital Cancer Center at Sturgeon Bay
- University Health Network-Princess Margaret Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Active Comparator
Experimental
Arm 1 (nivolumab, cabozantinib)
Arm 2 (nivolumab, placebo)
Arm 3 (nivolumab, cabozantinib)
Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study.
Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study.
Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycle in the absence of disease progression or unacceptable toxicity. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study.