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Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery

Primary Purpose

Anal Melanoma, Bladder Melanoma, Cervical Melanoma

Status
Suspended
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cabozantinib S-malate
Computed Tomography
Magnetic Resonance Imaging
Nivolumab
Placebo Administration
Positron Emission Tomography
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anal Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Arm 1 (nivolumab, cabozantinib)

Arm 2 (nivolumab, placebo)

Arm 3 (nivolumab, cabozantinib)

Arm Description

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.

Outcomes

Primary Outcome Measures

Recurrence free survival (RFS)
Will evaluate RFS of single agent adjuvant nivolumab plus placebo compared to the combination treatment of adjuvant nivolumab plus cabozantinib in patients with resected mucosal melanoma.

Secondary Outcome Measures

Overall survival (OS)
Will be evaluated utilizing the Kaplan-Meier (KM) method and, when appropriate, cox proportional hazards models. Median OS is calculated (along with 95% Confidence intervals) using the KM method. A Cox proportional hazards model is built to compare arms 1 and 2 with respect to OS.
RFS
Median RFS will be calculated (along with 95% Confidence intervals) using the KM method. A Cox proportional hazards model will also be built to compare arms 1 and 2 with respect to RFS, with and without stratifying for PD-L1 categorization. For non-resected cohort, If a patient in this group has surgery, their PFS data will be censored at the time of surgery.
Progression free survival (PFS)
Will be evaluated in multiple settings utilizing the KM method and, when appropriate, cox proportional hazards models.
Overall response rate (Arm 3)
Duration of response (Arm 3)
A KM analysis is performed to calculate the median duration of response and 95% confidence intervals are constructed.
Incidence of adverse events
The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5.0. The frequency and percentage of grade 3+ adverse events will be summarized.

Full Information

First Posted
November 5, 2021
Last Updated
October 14, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05111574
Brief Title
Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery
Official Title
A Randomized Phase II Trial of Adjuvant Nivolumab With or Without Cabozantinib in Patients With Resected Mucosal Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Suspended
Why Stopped
Other - Crossed AE stopping rule
Study Start Date
August 11, 2022 (Actual)
Primary Completion Date
December 19, 2023 (Anticipated)
Study Completion Date
December 19, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial tests whether nivolumab in combination with cabozantinib works in patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving nivolumab in combination with cabozantinib could prevent cancer from returning.
Detailed Description
PRIMARY OBJECTIVE: I. To compare the efficacy of adjuvant nivolumab (480 mg every [q]4 weeks) versus nivolumab plus cabozantinib s-malate (cabozantinib) (40 mg daily) in patients with mucosal melanoma. SECONDARY OBJECTIVES: I. To compare overall survival between the two adjuvant therapies. II. To evaluate the adverse effects in each arm. III. To assess the correlation between PD-L1 expression in tumor cells with survival (recurrence free survival [RFS] and overall survival [OS]). IV. To evaluate the overall response rate (ORR), duration of response (DOR), progression free survival (PFS), and OS of nivolumab plus cabozantinib in patients who cannot undergo gross total resection of disease or have metastatic disease at baseline. V. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue. OUTLINE: Patients whose tumor has been fully removed by surgery are randomized to Arm 1 or Arm 2. Patients whose tumor has not been fully removed by surgery or has spread are assigned to Arm 3. ARM 1: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and cabozantinib orally (PO) once daily (QD) of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. ARM 2: 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. ARM 3: 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 computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT at baseline, CT and MRI may be repeated every 6 months on study. After completion of study treatment, patients are followed up every 3 months until disease progression, and then every 6 months for up to 5 years from registration or until death.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anal Melanoma, Bladder Melanoma, Cervical Melanoma, Esophageal Melanoma, Gallbladder Melanoma, Mucosal Melanoma, Mucosal Melanoma of the Head and Neck, Mucosal Melanoma of the Urinary System, Oral Cavity Mucosal Melanoma, Penile Mucosal Melanoma, Rectal Melanoma, Recurrent Mucosal Melanoma, Sinonasal Mucosal Melanoma, Stage II Vulvar Cancer AJCC v8, Stage III Vulvar Cancer AJCC v8, Stage IV Vulvar Cancer AJCC v8, Urethral Melanoma, Vaginal Melanoma, Vulvar Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
99 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 (nivolumab, cabozantinib)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2 (nivolumab, placebo)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm 3 (nivolumab, cabozantinib)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cabozantinib S-malate
Other Intervention Name(s)
BMS-907351, Cabometyx, Cometriq, XL-184, XL184
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
ABP 206, BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Placebo Administration
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT
Intervention Description
Undergo PET
Primary Outcome Measure Information:
Title
Recurrence free survival (RFS)
Description
Will evaluate RFS of single agent adjuvant nivolumab plus placebo compared to the combination treatment of adjuvant nivolumab plus cabozantinib in patients with resected mucosal melanoma.
Time Frame
Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
Will be evaluated utilizing the Kaplan-Meier (KM) method and, when appropriate, cox proportional hazards models. Median OS is calculated (along with 95% Confidence intervals) using the KM method. A Cox proportional hazards model is built to compare arms 1 and 2 with respect to OS.
Time Frame
Number of days from registration until death (due to any cause, assessed up to 5 years
Title
RFS
Description
Median RFS will be calculated (along with 95% Confidence intervals) using the KM method. A Cox proportional hazards model will also be built to compare arms 1 and 2 with respect to RFS, with and without stratifying for PD-L1 categorization. For non-resected cohort, If a patient in this group has surgery, their PFS data will be censored at the time of surgery.
Time Frame
Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years
Title
Progression free survival (PFS)
Description
Will be evaluated in multiple settings utilizing the KM method and, when appropriate, cox proportional hazards models.
Time Frame
Number of days from registration until either radiographic or clinical progression or death (due to any cause), assessed up to 5 years
Title
Overall response rate (Arm 3)
Time Frame
Up to 5 years
Title
Duration of response (Arm 3)
Description
A KM analysis is performed to calculate the median duration of response and 95% confidence intervals are constructed.
Time Frame
Time from the first evidence of response until progression, assessed up to 5 years
Title
Incidence of adverse events
Description
The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5.0. The frequency and percentage of grade 3+ adverse events will be summarized.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 Urine protein =< 1 OR UPC (urine protein/creatinine) ratio < 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander N Shoushtari
Organizational Affiliation
Alliance for Clinical Trials in Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sutter Auburn Faith Hospital
City
Auburn
State/Province
California
ZIP/Postal Code
95602
Country
United States
Facility Name
Alta Bates Summit Medical Center-Herrick Campus
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
Keck Medicine of USC Koreatown
City
Los Angeles
State/Province
California
ZIP/Postal Code
90020
Country
United States
Facility Name
Los Angeles County-USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Memorial Medical Center
City
Modesto
State/Province
California
ZIP/Postal Code
95355
Country
United States
Facility Name
USC Norris Oncology/Hematology-Newport Beach
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Palo Alto Medical Foundation Health Care
City
Palo Alto
State/Province
California
ZIP/Postal Code
94301
Country
United States
Facility Name
Stanford Cancer Institute Palo Alto
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Sutter Roseville Medical Center
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
Sutter Medical Center Sacramento
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
California Pacific Medical Center-Pacific Campus
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Palo Alto Medical Foundation-Sunnyvale
City
Sunnyvale
State/Province
California
ZIP/Postal Code
94086
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Aventura
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Coral Gables
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33146
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33442
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Plantation
City
Plantation
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Facility Name
Saint Alphonsus Cancer Care Center-Boise
City
Boise
State/Province
Idaho
ZIP/Postal Code
83706
Country
United States
Facility Name
Saint Alphonsus Cancer Care Center-Caldwell
City
Caldwell
State/Province
Idaho
ZIP/Postal Code
83605
Country
United States
Facility Name
Kootenai Health - Coeur d'Alene
City
Coeur d'Alene
State/Province
Idaho
ZIP/Postal Code
83814
Country
United States
Facility Name
Saint Alphonsus Cancer Care Center-Nampa
City
Nampa
State/Province
Idaho
ZIP/Postal Code
83687
Country
United States
Facility Name
Kootenai Clinic Cancer Services - Post Falls
City
Post Falls
State/Province
Idaho
ZIP/Postal Code
83854
Country
United States
Facility Name
Kootenai Cancer Clinic
City
Sandpoint
State/Province
Idaho
ZIP/Postal Code
83864
Country
United States
Facility Name
Rush - Copley Medical Center
City
Aurora
State/Province
Illinois
ZIP/Postal Code
60504
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Carle at The Riverfront
City
Danville
State/Province
Illinois
ZIP/Postal Code
61832
Country
United States
Facility Name
Cancer Care Specialists of Illinois - Decatur
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
Decatur Memorial Hospital
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
Carle Physician Group-Effingham
City
Effingham
State/Province
Illinois
ZIP/Postal Code
62401
Country
United States
Facility Name
Crossroads Cancer Center
City
Effingham
State/Province
Illinois
ZIP/Postal Code
62401
Country
United States
Facility Name
Carle Physician Group-Mattoon/Charleston
City
Mattoon
State/Province
Illinois
ZIP/Postal Code
61938
Country
United States
Facility Name
Southern Illinois University School of Medicine
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Springfield Clinic
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Memorial Medical Center
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62781
Country
United States
Facility Name
Carle Cancer Center
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Rush-Copley Healthcare Center
City
Yorkville
State/Province
Illinois
ZIP/Postal Code
60560
Country
United States
Facility Name
Mary Greeley Medical Center
City
Ames
State/Province
Iowa
ZIP/Postal Code
50010
Country
United States
Facility Name
McFarland Clinic - Ames
City
Ames
State/Province
Iowa
ZIP/Postal Code
50010
Country
United States
Facility Name
McFarland Clinic - Boone
City
Boone
State/Province
Iowa
ZIP/Postal Code
50036
Country
United States
Facility Name
McFarland Clinic - Trinity Cancer Center
City
Fort Dodge
State/Province
Iowa
ZIP/Postal Code
50501
Country
United States
Facility Name
McFarland Clinic - Jefferson
City
Jefferson
State/Province
Iowa
ZIP/Postal Code
50129
Country
United States
Facility Name
McFarland Clinic - Marshalltown
City
Marshalltown
State/Province
Iowa
ZIP/Postal Code
50158
Country
United States
Facility Name
Bronson Battle Creek
City
Battle Creek
State/Province
Michigan
ZIP/Postal Code
49017
Country
United States
Facility Name
Spectrum Health at Butterworth Campus
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Trinity Health Grand Rapids Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Bronson Methodist Hospital
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
West Michigan Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
Ascension Borgess Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49009
Country
United States
Facility Name
Trinity Health Muskegon Hospital
City
Muskegon
State/Province
Michigan
ZIP/Postal Code
49444
Country
United States
Facility Name
Cancer and Hematology Centers of Western Michigan - Norton Shores
City
Norton Shores
State/Province
Michigan
ZIP/Postal Code
49444
Country
United States
Facility Name
Spectrum Health Reed City Hospital
City
Reed City
State/Province
Michigan
ZIP/Postal Code
49677
Country
United States
Facility Name
Marie Yeager Cancer Center
City
Saint Joseph
State/Province
Michigan
ZIP/Postal Code
49085
Country
United States
Facility Name
Munson Medical Center
City
Traverse City
State/Province
Michigan
ZIP/Postal Code
49684
Country
United States
Facility Name
University of Michigan Health - West
City
Wyoming
State/Province
Michigan
ZIP/Postal Code
49519
Country
United States
Facility Name
Minnesota Oncology - Burnsville
City
Burnsville
State/Province
Minnesota
ZIP/Postal Code
55337
Country
United States
Facility Name
Mercy Hospital
City
Coon Rapids
State/Province
Minnesota
ZIP/Postal Code
55433
Country
United States
Facility Name
Fairview Southdale Hospital
City
Edina
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Facility Name
Abbott-Northwestern Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Park Nicollet Clinic - Saint Louis Park
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
United Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Parkland Health Center - Farmington
City
Farmington
State/Province
Missouri
ZIP/Postal Code
63640
Country
United States
Facility Name
Missouri Baptist Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63131
Country
United States
Facility Name
Sainte Genevieve County Memorial Hospital
City
Sainte Genevieve
State/Province
Missouri
ZIP/Postal Code
63670
Country
United States
Facility Name
Missouri Baptist Sullivan Hospital
City
Sullivan
State/Province
Missouri
ZIP/Postal Code
63080
Country
United States
Facility Name
Missouri Baptist Outpatient Center-Sunset Hills
City
Sunset Hills
State/Province
Missouri
ZIP/Postal Code
63127
Country
United States
Facility Name
Community Hospital of Anaconda
City
Anaconda
State/Province
Montana
ZIP/Postal Code
59711
Country
United States
Facility Name
Billings Clinic Cancer Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Bozeman Deaconess Hospital
City
Bozeman
State/Province
Montana
ZIP/Postal Code
59715
Country
United States
Facility Name
Benefis Healthcare- Sletten Cancer Institute
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Kalispell Regional Medical Center
City
Kalispell
State/Province
Montana
ZIP/Postal Code
59901
Country
United States
Facility Name
Community Medical Hospital
City
Missoula
State/Province
Montana
ZIP/Postal Code
59804
Country
United States
Facility Name
Memorial Sloan Kettering Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
NYU Winthrop Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Laura and Isaac Perlmutter Cancer Center at NYU Langone
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Dayton Physician LLC-Miami Valley Hospital North
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45415
Country
United States
Facility Name
Kettering Medical Center
City
Kettering
State/Province
Ohio
ZIP/Postal Code
45429
Country
United States
Facility Name
Cancer Centers of Southwest Oklahoma Research
City
Lawton
State/Province
Oklahoma
ZIP/Postal Code
73505
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Saint Alphonsus Medical Center-Ontario
City
Ontario
State/Province
Oregon
ZIP/Postal Code
97914
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh Cancer Institute (UPCI)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Asplundh Cancer Pavilion
City
Willow Grove
State/Province
Pennsylvania
ZIP/Postal Code
19090
Country
United States
Facility Name
Avera Cancer Institute
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
VCU Massey Cancer Center at Stony Point
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23235
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
HSHS Sacred Heart Hospital
City
Eau Claire
State/Province
Wisconsin
ZIP/Postal Code
54701
Country
United States
Facility Name
Saint Vincent Hospital Cancer Center Green Bay
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54301
Country
United States
Facility Name
Saint Vincent Hospital Cancer Center at Saint Mary's
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54303
Country
United States
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Saint Vincent Hospital Cancer Center at Oconto Falls
City
Oconto Falls
State/Province
Wisconsin
ZIP/Postal Code
54154
Country
United States
Facility Name
Saint Vincent Hospital Cancer Center at Sheboygan
City
Sheboygan
State/Province
Wisconsin
ZIP/Postal Code
53081
Country
United States
Facility Name
Saint Vincent Hospital Cancer Center at Sturgeon Bay
City
Sturgeon Bay
State/Province
Wisconsin
ZIP/Postal Code
54235-1495
Country
United States
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm

Learn more about this trial

Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery

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