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

August 1, 2026 updated by: National Cancer Institute (NCI)

A Randomized Phase II Trial of Adjuvant Nivolumab With or Without Cabozantinib in Patients With Resected Mucosal Melanoma

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 cycles in the absence of disease progression or unacceptable toxicity.

Patients undergo echocardiogram (ECHO) during screening and as clinically indicated throughout the trial. 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. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial.

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.

Study Type

Interventional

Enrollment (Estimated)

101

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital and Cancer Center-General Campus
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network-Princess Margaret Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Odette Cancer Centre- Sunnybrook Health Sciences Centre
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
  • United States
    • California
      • Auburn, California, United States, 95602
        • Sutter Auburn Faith Hospital
      • Berkeley, California, United States, 94704
        • Alta Bates Summit Medical Center-Herrick Campus
      • Fremont, California, United States, 94538
        • Palo Alto Medical Foundation-Fremont
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90020
        • Keck Medicine of USC Koreatown
      • Los Angeles, California, United States, 90033
        • Los Angeles General Medical Center
      • Modesto, California, United States, 95355
        • Memorial Medical Center
      • Newport Beach, California, United States, 92663
        • USC Norris Oncology/Hematology-Newport Beach
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • Palo Alto, California, United States, 94301
        • Palo Alto Medical Foundation Health Care
      • Roseville, California, United States, 95661
        • Sutter Roseville Medical Center
      • Sacramento, California, United States, 95816
        • Sutter Medical Center Sacramento
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center-Pacific Campus
      • San Mateo, California, United States, 94401
        • Mills Health Center
      • Santa Cruz, California, United States, 95065
        • Palo Alto Medical Foundation-Santa Cruz
      • Santa Rosa, California, United States, 95403
        • Sutter Pacific Medical Foundation
      • Sunnyvale, California, United States, 94086
        • Palo Alto Medical Foundation-Sunnyvale
      • Vallejo, California, United States, 94589
        • Sutter Solano Medical Center/Cancer Center
    • Colorado
      • Englewood, Colorado, United States, 80113
        • The Melanoma and Skin Cancer Institute
    • Florida
      • Aventura, Florida, United States, 33180
        • UM Sylvester Comprehensive Cancer Center at Aventura
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Plantation, Florida, United States, 33324
        • UM Sylvester Comprehensive Cancer Center at Plantation
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
      • Caldwell, Idaho, United States, 83605
        • Saint Alphonsus Cancer Care Center-Caldwell
      • Coeur d'Alene, Idaho, United States, 83814
        • Kootenai Health - Coeur d'Alene
      • Nampa, Idaho, United States, 83687
        • Saint Alphonsus Cancer Care Center-Nampa
      • Post Falls, Idaho, United States, 83854
        • Kootenai Clinic Cancer Services - Post Falls
      • Sandpoint, Idaho, United States, 83864
        • Kootenai Clinic Cancer Services - Sandpoint
    • Illinois
      • Aurora, Illinois, United States, 60504
        • Rush-Copley Medical Center
      • Centralia, Illinois, United States, 62801
        • Centralia Oncology Clinic
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Danville, Illinois, United States, 61832
        • Carle at The Riverfront
      • DeKalb, Illinois, United States, 60115
        • Northwestern Medicine Cancer Center Kishwaukee
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Cancer Care Specialists of Illinois - Decatur
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Effingham, Illinois, United States, 62401
        • Carle Physician Group-Effingham
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Glenview, Illinois, United States, 60026
        • Northwestern Medicine Glenview Outpatient Center
      • Grayslake, Illinois, United States, 60030
        • Northwestern Medicine Grayslake Outpatient Center
      • Lake Forest, Illinois, United States, 60045
        • Northwestern Medicine Lake Forest Hospital
      • Mattoon, Illinois, United States, 61938
        • Carle Physician Group-Mattoon/Charleston
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • Orland Park, Illinois, United States, 60462
        • Northwestern Medicine Orland Park
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic
      • Springfield, Illinois, United States, 62781
        • Springfield Memorial Hospital
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
      • Yorkville, Illinois, United States, 60560
        • Rush-Copley Healthcare Center
    • Iowa
      • Ames, Iowa, United States, 50010
        • Mary Greeley Medical Center
      • Ames, Iowa, United States, 50010
        • McFarland Clinic - Ames
      • Ankeny, Iowa, United States, 50023
        • UI Health Care Mission Cancer and Blood - Ankeny Clinic
      • Boone, Iowa, United States, 50036
        • McFarland Clinic - Boone
      • Clive, Iowa, United States, 50325
        • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50314
        • UI Health Care Mission Cancer and Blood - Laurel Clinic
      • Fort Dodge, Iowa, United States, 50501
        • McFarland Clinic - Trinity Cancer Center
      • Jefferson, Iowa, United States, 50129
        • McFarland Clinic - Jefferson
      • Marshalltown, Iowa, United States, 50158
        • McFarland Clinic - Marshalltown
      • Waukee, Iowa, United States, 50263
        • UI Health Care Mission Cancer and Blood - Waukee Clinic
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Michigan
      • Battle Creek, Michigan, United States, 49017
        • Bronson Battle Creek
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Grand Rapids Hospital
      • Grand Rapids, Michigan, United States, 49503
        • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49009
        • Beacon Kalamazoo Cancer Center
      • Muskegon, Michigan, United States, 49444
        • Trinity Health Muskegon Hospital
      • Niles, Michigan, United States, 49120
        • Corewell Health Lakeland Hospitals - Niles Hospital
      • Norton Shores, Michigan, United States, 49444
        • Cancer and Hematology Centers of Western Michigan - Norton Shores
      • Reed City, Michigan, United States, 49677
        • Corewell Health Reed City Hospital
      • Saint Joseph, Michigan, United States, 49085
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
      • Wyoming, Michigan, United States, 49519
        • University of Michigan Health - West
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Minnesota Oncology - Burnsville
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy Hospital
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Hospital
      • Minneapolis, Minnesota, United States, 55407
        • Abbott-Northwestern Hospital
      • Robbinsdale, Minnesota, United States, 55422
        • North Memorial Medical Health Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
      • Saint Louis Park, Minnesota, United States, 55416
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
    • Missouri
      • Farmington, Missouri, United States, 63640
        • Parkland Health Center - Farmington
      • Sainte Genevieve, Missouri, United States, 63670
        • Sainte Genevieve County Memorial Hospital
      • St Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Sullivan, Missouri, United States, 63080
        • Missouri Baptist Sullivan Hospital
    • Montana
      • Anaconda, Montana, United States, 59711
        • Community Hospital of Anaconda
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Bozeman, Montana, United States, 59715
        • Bozeman Health Deaconess Hospital
      • Great Falls, Montana, United States, 59405
        • Benefis Sletten Cancer Institute
      • Kalispell, Montana, United States, 59901
        • Logan Health Medical Center
      • Missoula, Montana, United States, 59804
        • Community Medical Center
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Basking Ridge
    • New York
      • Camillus, New York, United States, 13031
        • Hematology Oncology Associates of CNY at Camillus
      • East Syracuse, New York, United States, 13057
        • Hematology Oncology Associates of Central New York-East Syracuse
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • Mineola, New York, United States, 11501
        • NYU Langone Hospital - Long Island
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • Ohio
      • Centerville, Ohio, United States, 45459
        • Miami Valley Hospital South
      • Cincinnati, Ohio, United States, 45220
        • Good Samaritan Hospital - Cincinnati
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospital
      • Dayton, Ohio, United States, 45415
        • Miami Valley Hospital North
      • Dayton, Ohio, United States, 45415
        • Dayton Physician LLC - Englewood
      • Dayton, Ohio, United States, 45409
        • Premier Blood and Cancer Center
      • Franklin, Ohio, United States, 45005-1066
        • Atrium Medical Center-Middletown Regional Hospital
      • Greenville, Ohio, United States, 45331
        • Miami Valley Cancer Care and Infusion
      • Kettering, Ohio, United States, 45429
        • Kettering Medical Center
      • Troy, Ohio, United States, 45373
        • Upper Valley Medical Center
    • Oklahoma
      • Lawton, Oklahoma, United States, 73505
        • Cancer Centers of Southwest Oklahoma Research
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Ontario, Oregon, United States, 97914
        • Saint Alphonsus Cancer Care Center-Ontario
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
      • Willow Grove, Pennsylvania, United States, 19090
        • Asplundh Cancer Pavilion
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Rapid City Regional Hospital
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23235
        • VCU Massey Cancer Center at Stony Point
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
        • Marshfield Medical Center-EC Cancer Center
      • Eau Claire, Wisconsin, United States, 54701
        • HSHS Sacred Heart Hospital
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital Cancer Center Green Bay
      • Green Bay, Wisconsin, United States, 54303
        • Saint Vincent Hospital Cancer Center at Saint Mary's
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Madison, Wisconsin, United States, 53718
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Minocqua, Wisconsin, United States, 54548
        • Marshfield Medical Center - Minocqua
      • Oconto Falls, Wisconsin, United States, 54154
        • Saint Vincent Hospital Cancer Center at Oconto Falls
      • Rice Lake, Wisconsin, United States, 54868
        • Marshfield Medical Center-Rice Lake
      • Sheboygan, Wisconsin, United States, 53081
        • Saint Vincent Hospital Cancer Center at Sheboygan
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Sturgeon Bay, Wisconsin, United States, 54235-1495
        • Saint Vincent Hospital Cancer Center at Sturgeon Bay
      • Weston, Wisconsin, United States, 54476
        • Marshfield Medical Center - Weston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

    • Report is required for randomization of resection R0 or R1 patients
    • Testing must be started in Step 0 but results can be reported after registration for resection R2 patients

  • 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 - Sinonasal (including nasopharynx): any primary lesion; Nasal or oral cavity; pT4a or above, given slightly improved OS

        • NOTE: Conjunctival: does not meet the qualification for eligibility
      • 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- American Joint Committee on Cancer (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. Exceptions may allow for adjuvant no evidence of disease (NED) cancers undergoing hormone based therapy may be eligible pending the other eligibility criteria are met and the principal investigator (PI) affirms the hormonal agent would not change the melanoma response.
    • Any radiation must have completed 28 days prior to randomization and the patient must have adequately recovered from its effects.
    • For resectable patients only: Surgery must have completed 28 days prior to randomization.
    • For resectable patients only: 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
  • 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 electrocardiograms (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 5 days prior to the start of study treatment.
    • Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 5 days prior to the start of study treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1 (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 undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • MDX 1106
  • MDX1106
  • BMS 936558
  • ABP 206
  • Nivolumab Biosimilar ABP 206
  • BCD-263
  • Nivolumab Biosimilar BCD-263
  • BMS936558
  • ONO 4538
  • ONO4538
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Drug: Cabozantinib S-malate
Given PO
Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184
  • XL 184
Procedure: Biospecimen Collection
Undergo blood and tissue sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Bone Scan
Undergo bone scan
Other Names:
  • Bone Scintigraphy
Procedure: Echocardiography Test
Undergo ECHO
Other Names:
  • Echocardiography
  • EC
Active Comparator: Arm 2 (nivolumab, placebo)
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 undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • MDX 1106
  • MDX1106
  • BMS 936558
  • ABP 206
  • Nivolumab Biosimilar ABP 206
  • BCD-263
  • Nivolumab Biosimilar BCD-263
  • BMS936558
  • ONO 4538
  • ONO4538
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Drug: Placebo Administration
Given PO
Procedure: Biospecimen Collection
Undergo blood and tissue sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Bone Scan
Undergo bone scan
Other Names:
  • Bone Scintigraphy
Procedure: Echocardiography Test
Undergo ECHO
Other Names:
  • Echocardiography
  • EC
Experimental: Arm 3 (nivolumab, cabozantinib)
Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • MDX 1106
  • MDX1106
  • BMS 936558
  • ABP 206
  • Nivolumab Biosimilar ABP 206
  • BCD-263
  • Nivolumab Biosimilar BCD-263
  • BMS936558
  • ONO 4538
  • ONO4538
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Drug: Cabozantinib S-malate
Given PO
Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184
  • XL 184
Procedure: Biospecimen Collection
Undergo blood and tissue sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Bone Scan
Undergo bone scan
Other Names:
  • Bone Scintigraphy
Procedure: Echocardiography Test
Undergo ECHO
Other Names:
  • Echocardiography
  • EC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence free survival (RFS)
Time Frame: Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years
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.
Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Number of days from registration until death (due to any cause, assessed up to 5 years
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.
Number of days from registration until death (due to any cause, assessed up to 5 years
Duration of response (Arm 3)
Time Frame: Time from the first evidence of response until progression, assessed up to 5 years
A KM analysis is performed to calculate the median duration of response and 95% confidence intervals are constructed.
Time from the first evidence of response until progression, assessed up to 5 years
Incidence of adverse events
Time Frame: Up to 5 years
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.
Up to 5 years
Objective response rate (Arm 3)
Time Frame: Up to 5 years
Will assess this endpoint utilizing a two-stage Simon that looks to improve from a rate of 20% to 47%.
Up to 5 years
RFS
Time Frame: Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years
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 RFS data will be censored at the time of surgery.
Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years
Progression free survival
Time Frame: Number of days from registration until either radiographic or clinical progression or death (due to any cause), assessed up to 5 years
Will be evaluated in multiple settings utilizing the KM method and, when appropriate, cox proportional hazards models.
Number of days from registration until either radiographic or clinical progression or death (due to any cause), assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Alexander N Shoushtari, Alliance for Clinical Trials in Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 11, 2022

Primary Completion (Estimated)

July 15, 2027

Study Completion (Estimated)

July 15, 2027

Study Registration Dates

First Submitted

November 5, 2021

First Submitted That Met QC Criteria

November 5, 2021

First Posted (Actual)

November 8, 2021

Study Record Updates

Last Update Posted (Actual)

August 4, 2026

Last Update Submitted That Met QC Criteria

August 1, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2021-11794 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180821 (U.S. NIH Grant/Contract)
  • A091903 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe