NCT03033576

Testing Treatment With Ipilimumab and Nivolumab Compared to Treatment With Ipilimumab Alone in Advanced Melanoma

A Phase II Randomized Study of Nivolumab (NSC-748726) With Ipilimumab (NSC-732442) or Ipilimumab Alone in Advanced Melanoma Patients Refractory to an Anti-PD1 or Anti-PD-L1 Agent

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 94 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well ipilimumab with or without nivolumab work in treating patients with melanoma that is stage IV or stage III and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVE: I. To compare progression free survival (PFS) of patients with advanced melanoma refractory to an anti-PD-1 or anti-PD-L1 agent, treated with combination therapy ipilimumab plus nivolumab versus ipilimumab alone. SECONDARY OBJECTIVES: I. To estimate difference in T-cell infiltrate between on-study biopsy samples of patients who respond to combination therapy (including confirmed and unconfirmed, complete and partial response per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1, in each treatment arm). II. To evaluate the objective response rate (ORR), defined as confirmed complete or partial response per RECIST 1.1, in each treatment arm. III. To evaluate the overall survival (OS) of patients in each treatment arm. IV. To evaluate the toxicity profile of patients in each treatment arm. TRANSLATIONAL OBJECTIVES: I. To assess the marginal prognostic value of baseline T-cell density, T-cell receptor (TCR) clonality, mutational load, messenger ribonucleic acid (mRNA) and other phenotypical expression levels, and circulating tumor deoxyribonucleic acid (DNA) in terms of response. II. To assess the joint prognostic value of T-cell density, TCR clonality, and mutational load, mRNA and other phenotypical expression levels, and circulating tumor DNA in terms of response. III. To identify T-cell poor subtype(s) that are associated with response. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 1 year.

Conditions

• Clinical Stage III Cutaneous Melanoma AJCC v8
• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Melanoma of Unknown Primary
• Mucosal Melanoma
• Unresectable Cutaneous Melanoma
• Unresectable Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	Ipilimumab	Given IV
BIOLOGICAL	Nivolumab	Given IV

Timeline

• Start date: 2017-10-23
• Primary completion: 2023-09-19
• Completion: 2024-03-20
• First posted: 2017-01-27
• Last updated: 2025-01-13
• Results posted: 2023-05-01

Locations

638 sites across 1 country: United States

Regulatory

• FDA-regulated drug study