Nivolumab with or without Cabozantinib for Mucosal Melanoma After Surgery
This study is testing if nivolumab, alone or with cabozantinib, can prevent mucosal melanoma from returning after surgery. Mucosal melanoma is a rare type of skin cancer that starts in moist linings of the body, like the mouth or bladder. Nivolumab is an immunotherapy that helps your body's immune system fight cancer. Cabozantinib works by blocking proteins that help cancer cells grow. The study aims to see which treatment is more effective at preventing the cancer from coming back. To join, you must have mucosal melanoma that has been removed by surgery, and your tumor tissue will be tested for a marker called PD-L1. The study is looking for 101 participants.
- Study design
- This is an interventional study, meaning participants will receive a specific treatment. It involves different groups receiving either nivolumab alone or nivolumab with cabozantinib, or a group for those whose cancer was not fully removed or has spread.
- What's involved
- Participants will undergo blood and tissue sample collection, bone scans, CT scans, and echocardiography tests. Treatment involves receiving nivolumab intravenously and/or cabozantinib by mouth, repeating every 28 days for up to 13 cycles.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will track how long participants live without the cancer returning (recurrence-free survival) for up to 5 years.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05111574
Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery
Active, Not Recruiting
PHASE2Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~101 participants
Updated 2026-08-04 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone ScanCabozantinib S-malateComputed TomographyEchocardiography TestMagnetic Resonance Imaging
At a glance
Recruiting sites
0 of 146 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Recurrence free survival (RFS)
Measured over Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years
Conditions
Where it's being run
146 sites across 23 statesIllinois22
California19
Wisconsin14
Michigan13
Ohio12
Iowa11
Minnesota9
New York7
Study leadership
- Alexander N Shoushtari · PRINCIPAL_INVESTIGATOR · Alliance for Clinical Trials in Oncology
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Histologically proven mucosal melanoma by local pathology
Central PD-L1 tumor tissue submission
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.
What this trial measures
- Recurrence free survival (RFS)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.