Overview

This trial is active, not recruiting.

Conditions recurrent melanoma, stage iii melanoma, stage iv melanoma
Treatments ipilimumab, sargramostim
Phase phase 2
Target CTLA-4
Sponsor National Cancer Institute (NCI)
Start date December 2010
End date February 2013
Trial size 245 participants
Trial identifier NCT01134614, E1608, NCI-2011-02039, U10CA021115

Summary

This randomized phase II trial is studying how well giving ipilimumab with or without sargramostim (GM-CSF) works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Ipilimumab works by activating the patient's immune system to fight cancer. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of treatment. It is not yet known whether giving ipilimumab together with sargramostim is more effective than ipilimumab alone in treating melanoma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
ARM A: Patients receive induction therapy comprising ipilimumab intravenously (IV) over 90 minutes on day 1 and sargramostim subcutaneously (SC) once daily on days 1-14. Treatment repeats every 21 days for 4 cycles. After 12 weeks of induction treatment, anti-tumor response is assessed and patients then receive maintenance therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment with ipilimumab repeats every 12 weeks and treatment with sargramostim repeats every 21 days. After 12 weeks of maintenance therapy, anti-tumor response is reassessed and patients with responsive or stable disease then continue maintenance therapy until disease progression or unacceptable toxicity.
ipilimumab Anti-CTLA-4 monoclonal antibody
Given IV
sargramostim Granulocyte-macrophage colony stimulating factor (GM-CSF)
Given SC
(Experimental)
ARM B: Patients receive induction therapy comprising ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles. After 12 weeks of induction treatment, anti-tumor response is assessed and patients then receive maintenance therapy of ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 12 weeks. After 12 weeks of maintenance therapy, anti-tumor response is reassessed and courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
ipilimumab Anti-CTLA-4 monoclonal antibody
Given IV

Primary Outcomes

Measure
Overall Survival
time frame: Assessed every 3 months for 2 years, then every 6 months for 3 years

Secondary Outcomes

Measure
Progression-free Survival (PFS)
time frame: Assessed every 3 months for 2 years, then every 6 months for 3 years
Proportion of Patients With Objective Response
time frame: Assessed every 3 months for 2 years, then every 6 months for 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed metastatic melanoma - Unresectable stage III or IV disease - For unknown primary disease, diagnosis of metastatic disease by cytology FNA is not acceptable - Measurable disease - ECOG performance status 0-1 - White blood count (WBC) ≥ 2,000/μL - Absolute neutrophil count (ANC) ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Hemoglobin ≥ 8 g/dL - Creatinine ≤ 3.0 times upper limit of normal (ULN) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN - Bilirubin ≤ 3.0 times ULN (total bilirubin < 3.0 mg/dL for patients with Gilbert syndrome) - Negative pregnancy test - Fertile patients must use effective contraception during and for up to 12 weeks after completion of study - Patients with a history of autoimmune thyroiditis are eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy - At least 4 weeks since prior and no concurrent therapy with any of the following: - Aldesleukin (IL-2) - Interferon - Non-study immunotherapy regimens - Cytotoxic chemotherapy - Immunosuppressive agents - Other investigational therapies - Chronic use of systemic corticosteroids - Concurrent inhaled or topical steroids allowed - Concurrent physiologic replacement doses of corticosteroids allowed Exclusion Criteria: - More than 1 prior investigational therapy or systemic therapeutic regimen, including any of the following: - Chemotherapy - Biological therapy - Biochemotherapy - Investigational treatment - History of central nervous system (CNS) metastases - Pregnant or nursing - HIV infection - Active infection with hepatitis B virus - Active or chronic infection with hepatitis C virus - Underlying medical or psychiatric condition that, in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea - Concurrent medical condition requiring the use of systemic steroids - Prior treatment with ipilimumab or CD137 agonistor or CTLA-4 inhibitor or agonist - Other malignancy with the past 2 years except adequately treated and cured basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix - History of autoimmune disease, including any of the following: - Inflammatory bowel disease - Symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis[scleroderma]) - Systemic lupus erythematosus - Autoimmune vasculitis (e.g., Wegener granulomatosis) - Motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis) - Prior non-oncology vaccine therapy for the prevention of infectious disease within the past 28 days or after any dose of ipilimumab - Other systemic or local anticancer medications

Additional Information

Official title A Phase II Trial of GM-CSF Protein Plus Ipilimumab in Patients With Advanced Melanoma
Description PRIMARY OBJECTIVES: I. To evaluate the overall survival of patients with advanced melanoma treated with ipilimumab with versus without sargramostim. SECONDARY OBJECTIVES: I. To evaluate the progression-free survival of patients treated with these regimens. II. To evaluate the response rate in patients treated with these regimens. III. To evaluate the safety and tolerability of these regimens in these patients. IV. To explore prospectively the utility of immune-related response criteria (irRC) of patients receiving ipilimumab. OUTLINE: This is a multicenter study. Patients are stratified according to disease stage (unresectable vs M1a/1b vs M1c) and prior therapy (none vs interferon vs one investigational therapy or one systemic therapeutic regimen). Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive induction therapy comprising ipilimumab intravenously (IV) over 90 minutes on day 1 and sargramostim subcutaneously (SC) once daily on days 1-14. Treatment repeats every 21 days for 4 cycles. After 12 weeks of induction treatment, anti-tumor response is assessed and patients then receive maintenance therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment with ipilimumab repeats every 12 weeks and treatment with sargramostim repeats every 21 days. After 12 weeks of maintenance therapy, anti-tumor response is reassessed and patients with responsive or stable disease then continue maintenance therapy until disease progression or unacceptable toxicity. ARM B: Patients receive induction therapy comprising ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles. After 12 weeks of induction treatment, anti-tumor response is assessed and patients then receive maintenance therapy of ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 12 weeks. After 12 weeks of maintenance therapy, anti-tumor response is reassessed and courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).