Anal MelanomaPhase 2NCT05111574
Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery
A Phase 2 study testing Biospecimen Collection, Bone Scan and Cabozantinib S-malate in people with Anal Melanoma and Bladder Melanoma, run by National Cancer Institute (NCI) at 146 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anal Melanoma, Bladder Melanoma, Cervical Melanoma
- What is being tested?
- Biospecimen Collection, Bone Scan and Cabozantinib S-malate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 146 sitesin 2 countries
- Study dates
- 11 Aug 2022to 15 Jul 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
None listed.
Trial locations and contacts
146 sites in 2 countries.
146 sites in 2 countries
United States142 sites
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
Community Hospital of Anaconda
Anaconda, Montana, 59711
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
Sutter Auburn Faith Hospital
Auburn, California, 95602
Rush-Copley Medical Center
Aurora, Illinois, 60504
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Bronson Battle Creek
Battle Creek, Michigan, 49017
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704
Billings Clinic Cancer Center
Billings, Montana, 59101
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
McFarland Clinic - Boone
Boone, Iowa, 50036
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Hematology Oncology Associates of CNY at Camillus
Camillus, New York, 13031
Miami Valley Hospital South
Centerville, Ohio, 45459
Centralia Oncology Clinic
Centralia, Illinois, 62801
Northwestern University
Chicago, Illinois, 60611
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220
Case Western Reserve University
Cleveland, Ohio, 44106
MetroHealth Medical Center
Cleveland, Ohio, 44109
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Mercy Hospital
Coon Rapids, Minnesota, 55433
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
Carle at The Riverfront
Danville, Illinois, 61832
Miami Valley Hospital
Dayton, Ohio, 45409
Premier Blood and Cancer Center
Dayton, Ohio, 45409
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415
Miami Valley Hospital North
Dayton, Ohio, 45415
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Hematology Oncology Associates of Central New York-East Syracuse
East Syracuse, New York, 13057
HSHS Sacred Heart Hospital
Eau Claire, Wisconsin, 54701
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Fairview Southdale Hospital
Edina, Minnesota, 55435
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
The Melanoma and Skin Cancer Institute
Englewood, Colorado, 80113
Parkland Health Center - Farmington
Farmington, Missouri, 63640
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Palo Alto Medical Foundation-Fremont
Fremont, California, 94538
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
Miami Valley Cancer Care and Infusion
Greenville, Ohio, 45331
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
UT MD Anderson Cancer Center
Houston, Texas, 77030
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Beacon Kalamazoo Cancer Center
Kalamazoo, Michigan, 49009
Logan Health Medical Center
Kalispell, Montana, 59901
Kettering Medical Center
Kettering, Ohio, 45429
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505
Keck Medicine of USC Koreatown
Los Angeles, California, 90020
Los Angeles General Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548
Community Medical Center
Missoula, Montana, 59804
Memorial Medical Center
Modesto, California, 95355
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan, 49120
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, 49444
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
Saint Vincent Hospital Cancer Center at Oconto Falls
Oconto Falls, Wisconsin, 54154
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462
Palo Alto Medical Foundation Health Care
Palo Alto, California, 94301
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
Corewell Health Reed City Hospital
Reed City, Michigan, 49677
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Sutter Roseville Medical Center
Roseville, California, 95661
Sutter Medical Center Sacramento
Sacramento, California, 95816
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670
California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Mills Health Center
San Mateo, California, 94401
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
Palo Alto Medical Foundation-Santa Cruz
Santa Cruz, California, 95065
Sutter Pacific Medical Foundation
Santa Rosa, California, 95403
Saint Vincent Hospital Cancer Center at Sheboygan
Sheboygan, Wisconsin, 53081
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Springfield Memorial Hospital
Springfield, Illinois, 62781
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin, 54235-1495
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California, 94086
Munson Medical Center
Traverse City, Michigan, 49684
Upper Valley Medical Center
Troy, Ohio, 45373
Carle Cancer Center
Urbana, Illinois, 61801
Sutter Solano Medical Center/Cancer Center
Vallejo, California, 94589
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
University of Michigan Health - West
Wyoming, Michigan, 49519
Rush-Copley Healthcare Center
Yorkville, Illinois, 60560
Canada4 sites
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Ottawa Hospital and Cancer Center-General Campus
Ottawa, Ontario, K1H 8L6
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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.
- Conditions
- Anal Melanoma, Bladder Melanoma, Cervical Melanoma, Esophageal Melanoma, Gallbladder Melanoma, Head and Neck Mucosal Melanoma
- Being tested
- Biospecimen Collection, Bone Scan, Cabozantinib S-malate, Computed Tomography, Echocardiography Test
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood and tissue sample collection
Bone ScanProcedure or surgery
Also called Bone Scintigraphy
Undergo bone scan
Cabozantinib S-malateDrug
Also called BMS-907351, Cabometyx, Cometriq, XL 184
Given PO
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
NivolumabBiological
Also called ABP 206, BCD-263, BMS 936558, BMS-936558
Given IV
Placebo AdministrationDrug
Given PO
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (nivolumab, cabozantinib) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Procedure: Positron Emission Tomography |
| Arm 2 (nivolumab, placebo) | Active comparator | 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. Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Placebo Administration; Procedure: Positron Emission Tomography |
| Arm 3 (nivolumab, cabozantinib) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Procedure: Positron Emission Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years
Secondary outcomes (6)
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.
Measured: Number of days from registration until death (due to any cause, assessed up to 5 years
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 RFS data will be censored at the time of surgery.
Measured: 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
Will be evaluated in multiple settings utilizing the KM method and, when appropriate, cox proportional hazards models.
Measured: Number of days from registration until either radiographic or clinical progression or death (due to any cause), assessed up to 5 years
Objective response rate (Arm 3)
Will assess this endpoint utilizing a two-stage Simon that looks to improve from a rate of 20% to 47%.
Measured: Up to 5 years
Duration of response (Arm 3)
A KM analysis is performed to calculate the median duration of response and 95% confidence intervals are constructed.
Measured: Time from the first evidence of response until progression, assessed up to 5 years
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.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2021
- Study start11 Aug 2022
- Primary completion15 Jul 2027 (estimated)
- Study completion15 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anal MelanomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 101 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alexander N Shoushtari, Principal investigator, Alliance for Clinical Trials in Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05111574
- Sponsor's protocol ID
- NCI-2021-11794
- Other IDs
- NCI-2021-11794, A091903, A091903, U10CA180821
- Status last verified
- Jul 2026
- First submitted
- 5 Nov 2021
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial of Adjuvant Nivolumab With or Without Cabozantinib in Patients With Resected Mucosal Melanoma
- ClinicalTrials.gov ID
- NCT05111574
- Acronym / sponsor ID
- NCI-2021-11794
- Conditions
- Anal Melanoma, Bladder Melanoma, Cervical Melanoma, Esophageal Melanoma, Gallbladder Melanoma, Head and Neck Mucosal Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 101 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 11 Aug 2022 (actual)
- Primary completion
- 15 Jul 2027 (estimated)
- Study completion
- 15 Jul 2027 (estimated)
- First posted
- 8 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (nivolumab, cabozantinib) | Experimental | Procedure: Biospecimen Collection, Procedure: Bone Scan, Drug: Cabozantinib S-malate, Procedure: Computed Tomography, Procedure: Echocardiography Test, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Procedure: Positron Emission TomographyPatients 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. |
| Arm 2 (nivolumab, placebo) | Active comparator | Procedure: Biospecimen Collection, Procedure: Bone Scan, Procedure: Computed Tomography, Procedure: Echocardiography Test, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Drug: Placebo Administration, Procedure: Positron Emission TomographyPatients 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. |
| Arm 3 (nivolumab, cabozantinib) | Experimental | Procedure: Biospecimen Collection, Procedure: Bone Scan, Drug: Cabozantinib S-malate, Procedure: Computed Tomography, Procedure: Echocardiography Test, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Procedure: Positron Emission TomographyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (69 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood and tissue sample collection | Procedure or surgery | Arm 1 (nivolumab, cabozantinib), Arm 2 (nivolumab, placebo), Arm 3 (nivolumab, cabozantinib) |
| Bone ScanAlso: Bone ScintigraphyUndergo bone scan | Procedure or surgery | Arm 1 (nivolumab, cabozantinib), Arm 2 (nivolumab, placebo), Arm 3 (nivolumab, cabozantinib) |
| Cabozantinib S-malateAlso: BMS-907351, Cabometyx, Cometriq, XL 184Given PO | Drug | Arm 1 (nivolumab, cabozantinib), Arm 3 (nivolumab, cabozantinib) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Arm 1 (nivolumab, cabozantinib), Arm 2 (nivolumab, placebo), Arm 3 (nivolumab, cabozantinib) |
| Echocardiography TestAlso: EC, EchocardiographyUndergo ECHO | Procedure or surgery | Arm 1 (nivolumab, cabozantinib), Arm 2 (nivolumab, placebo), Arm 3 (nivolumab, cabozantinib) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Arm 1 (nivolumab, cabozantinib), Arm 2 (nivolumab, placebo), Arm 3 (nivolumab, cabozantinib) |
| NivolumabAlso: ABP 206, BCD-263, BMS 936558, BMS-936558Given IV | Biological | Arm 1 (nivolumab, cabozantinib), Arm 2 (nivolumab, placebo), Arm 3 (nivolumab, cabozantinib) |
| Placebo AdministrationGiven PO | Drug | Arm 2 (nivolumab, placebo) |
| Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo PET | Procedure or surgery | Arm 1 (nivolumab, cabozantinib), Arm 2 (nivolumab, placebo), Arm 3 (nivolumab, cabozantinib) |
Primary outcome
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.
6 secondary outcomes
Overall survival (OS)
Time frame: Number of days from registration until death (due to any cause, assessed 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
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
Objective response rate (Arm 3)
Time frame: 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
Incidence of adverse events
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander N Shoushtari principal investigator
Alliance for Clinical Trials in Oncology
146 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biospecimen Collection, Bone Scan and Cabozantinib S-malate in people with Anal Melanoma and Bladder Melanoma, run by National Cancer Institute (NCI) at 146 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 69 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 146 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2026.