NCT05111574

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 101 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests whether nivolumab in combination with cabozantinib works in patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving nivolumab in combination with cabozantinib could prevent cancer from returning.

Detailed description

PRIMARY OBJECTIVE: I. To compare the efficacy of adjuvant nivolumab (480 mg every \[q\]4 weeks) versus nivolumab plus cabozantinib s-malate (cabozantinib) (40 mg daily) in patients with mucosal melanoma. SECONDARY OBJECTIVES: I. To compare overall survival between the two adjuvant therapies. II. To evaluate the adverse effects in each arm. III. To assess the correlation between PD-L1 expression in tumor cells with survival (recurrence free survival \[RFS\] and overall survival \[OS\]). IV. To evaluate the overall response rate (ORR), duration of response (DOR), progression free survival (PFS), and OS of nivolumab plus cabozantinib in patients who cannot undergo gross total resection of disease or have metastatic disease at baseline. V. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue. OUTLINE: Patients whose tumor has been fully removed by surgery are randomized to Arm 1 or Arm 2. Patients whose tumor has not been fully removed by surgery or has spread are assigned to Arm 3. ARM 1: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and cabozantinib orally (PO) once daily (QD) of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. ARM 3: Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 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
• Mucosal Melanoma
• Nasopharyngeal Mucosal Melanoma
• Oral Cavity Mucosal Melanoma
• Penile Mucosal Melanoma
• Rectal Melanoma
• Recurrent Mucosal Melanoma
• Sinonasal Mucosal Melanoma
• Urethral Melanoma
• Urinary System Mucosal Melanoma
• Vaginal Melanoma
• Vulvar Melanoma

Interventions

Type	Name	Description
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

Timeline

• Start date: 2022-08-11
• Primary completion: 2026-09-01
• Completion: 2026-09-01
• First posted: 2021-11-08
• Last updated: 2026-04-13

Locations

147 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study