NCT02339571

A Phase II/III Trial of Nivolumab, Ipilimumab, and GM-CSF in Patients With Advanced Melanoma

Randomized Phase II/III Study of Nivolumab Plus Ipilimumab Plus Sargramostim Versus Nivolumab Plus Ipilimumab in Patients With Unresectable Stage III or Stage IV Melanoma

• Status: Active Not Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 600 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II/III trial studies the side effects of nivolumab and ipilimumab when given together with or without sargramostim and to see how well they work in treating patients with stage III-IV melanoma that cannot be removed by surgery (unresectable) and that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). 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. Colony-stimulating factors, such as sargramostim, may increase the production of white blood cells. It is not yet known whether nivolumab and ipilimumab are more effective with or without sargramostim in treating patients with melanoma.

Detailed description

PRIMARY OBJECTIVE: I. To compare the overall survival (OS) of nivolumab/ipilimumab/sargramostim (GM-CSF) versus nivolumab/ipilimumab. SECONDARY OBJECTIVES: I. To evaluate progression free survival (PFS) of patients treated with nivolumab/ipilimumab/GM-CSF versus nivolumab/ipilimumab. II. To assess for differences in tolerability, specifically the rate of grade III or higher adverse events, between nivolumab/ipilimumab/GM-CSF versus nivolumab/ipilimumab. III. To evaluate immune-related response rate (based on immune-related response criteria) and response rate (based on Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) and to compare them. EXPLORATORY TOBACCO USE OBJECTIVES: I. To determine the effects of tobacco, operationalized as combustible tobacco (1a), other forms of tobacco (1b), and environmental tobacco exposure (ETS) (1c) on provider-reported cancer-treatment toxicity (adverse events \[both clinical and hematologic\] and dose modifications). II. To determine the effects of tobacco on patient-reported physical symptoms and psychological symptoms. III. To examine quitting behaviors and behavioral counseling/support and cessation medication utilization. IV. To explore the effect of tobacco use and exposure on treatment duration, relative dose intensity, and therapeutic benefit. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: INDUCTION THERAPY: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle, ipilimumab IV over 30 minutes on day 1 of each age, and sargramostim subcutaneously (SC) on days 1-14 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive nivolumab and sargramostim as in induction therapy. Patients with partial response (PR), stable disease (SD), or complete response (CR) at 24 weeks may continue maintenance therapy for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI), computed tomography (CT) scan, and blood sample collection throughout the study. Patients may also undergo a multigated acquisition (MUGA) during screening, as well as an echocardiography (ECHO) throughout the trial as clinically indicated. ARM B: INDUCTION THERAPY: Patients receive nivolumab and ipilimumab as in Arm I. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive nivolumab as in induction therapy. Patients with PR, SD, or CR at 24 weeks may continue maintenance therapy for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI, CT scan, and blood sample collection throughout the study. Patients may also undergo a MUGA during screening, as well as an ECHO throughout the trial as clinically indicated. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Conditions

• Stage III Cutaneous Melanoma AJCC v7
• Stage IV Cutaneous Melanoma AJCC v6 and v7

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT scan
PROCEDURE	Echocardiography Test	Undergo ECHO
BIOLOGICAL	Ipilimumab	Given IV
PROCEDURE	Magnetic Resonance Elastography	Undergo MRI
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
BIOLOGICAL	Nivolumab	Given IV
BIOLOGICAL	Sargramostim	Given SC

Timeline

• Start date: 2015-11-23
• Primary completion: 2033-06-30
• Completion: 2033-06-30
• First posted: 2015-01-15
• Last updated: 2026-04-13

Locations

766 sites across 1 country: United States

Regulatory

• FDA-regulated drug study