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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

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

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

Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery (NCT05111574) is a Phase 2 interventional studying Anal Melanoma and Bladder Melanoma, sponsored by National Cancer Institute (NCI). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Anal Melanoma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 101 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Anal Melanoma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

PROCEDURE

Biospecimen Collection

Undergo blood and tissue sample collection

PROCEDURE

Bone Scan

Undergo bone scan

DRUG

Cabozantinib S-malate

Given PO

PROCEDURE

Computed Tomography

Undergo CT

PROCEDURE

Echocardiography Test

Undergo ECHO

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

BIOLOGICAL

Nivolumab

Given IV

DRUG

Placebo Administration

Given PO

PROCEDURE

Positron Emission Tomography

Undergo PET

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Sutter Auburn Faith Hospital
Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
Palo Alto Medical Foundation-Fremont
Fremont, California, United States
Keck Medicine of USC Koreatown
Los Angeles, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Memorial Medical Center
Modesto, California, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, United States
Palo Alto Medical Foundation Health Care
Palo Alto, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Sutter Roseville Medical Center
Roseville, California, United States
Sutter Medical Center Sacramento
Sacramento, California, United States
California Pacific Medical Center-Pacific Campus
San Francisco, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Mills Health Center
San Mateo, California, United States
Palo Alto Medical Foundation-Santa Cruz
Santa Cruz, California, United States
Sutter Pacific Medical Foundation
Santa Rosa, California, United States
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California, United States
Sutter Solano Medical Center/Cancer Center
Vallejo, California, United States
The Melanoma and Skin Cancer Institute
Englewood, Colorado, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05111574), the sponsor (National Cancer Institute (NCI)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05111574 clinical trial studying?

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 pr… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT05111574?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05111574?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05111574. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05111574. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-07 · Data from ClinicalTrials.gov.