Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery
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Purpose
This randomized phase II trial is studying how well giving ipilimumab with or without sargramostim works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Colony-stimulating factors, such as sargramostim (GM-CSF), 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 know whether giving ipilimumab together with GM-CSF is more effective than ipilimumab alone in treating melanoma
| Condition | Intervention | Phase |
|---|---|---|
|
Recurrent Melanoma Stage III Melanoma Stage IV Melanoma |
Biological: ipilimumab Biological: sargramostim |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Trial of GM-CSF Protein Plus Ipilimumab in Patients With Advanced Melanoma |
- Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The method of Kaplan- Meir will be used.
- Progression-free survival [ Time Frame: From randomization to disease progression or death without progression, assessed up to 5 years ] [ Designated as safety issue: No ]The method of Kaplan- Meir will be used.
- Response rate using RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The Kappa statistics which measures the degree of agreement between the RECIST-based response and irRC will be estimated. McNemar's test will be used to evaluate the agreement between irRC and RECIST-based clinical response.
- Safety and tolerability assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Incidence data of specific toxicity type as well overall worst degree toxicity data will be summarized and compared between the two arms.
| Estimated Enrollment: | 220 |
| Study Start Date: | December 2010 |
| Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (ipilimumab and sargramostim)
Patients receive induction therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment repeats every 21 days for 4 courses. Patients with responsive or stable disease 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 in the absence of disease progression or unacceptable toxicity.
|
Biological: ipilimumab
Given IV
Other Names:
Biological: sargramostim
Given SC
Other Names:
|
|
Experimental: Arm II (ipilimumab)
Patients receive induction therapy comprising ipilimumab as in arm I. Patients with responsive or stable disease then receive maintenance therapy comprising ipilimumab IV as in arm I. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
|
Biological: ipilimumab
Given IV
Other Names:
|
Detailed 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). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive induction therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim subcutaneously (SC) once daily on days 1-14. Treatment repeats every 21 days for 4 courses. Patients with responsive or stable disease 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 in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive induction therapy comprising ipilimumab as in arm I. Patients with responsive or stable disease then receive maintenance therapy comprising ipilimumab IV as in arm I. 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
No more than 1 prior investigational therapy or systemic therapeutic regimen*, including any of the following:
- Chemotherapy
- Biological therapy
- Biochemotherapy
- Investigational treatment
- No CNS metastases
- ECOG performance status 0-1
- WBC ≥ 2,000/μL
- ANC ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 8 g/dL
- Creatinine ≤ 3.0 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Bilirubin ≤ 3.0 times ULN (total bilirubin < 3.0 mg/dL for patients with Gilbert syndrome)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for up to 12 weeks after completion of study
- No HIV infection
- No active infection with hepatitis B virus
- No active or chronic infection with hepatitis C virus
- No 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
No 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)
- Patients with a history of autoimmune thyroiditis are eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy
- No 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
- No concurrent medical condition requiring the use of systemic steroids
- No other concurrent CTLA-4 inhibitor or agonist or CD137 agonist
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
- No prior non-oncology vaccine therapy for the prevention of infectious disease within the past 28 days or after any dose of ipilimumab
- No prior ipilimumab, CD137agonist, or CTLA-4 inhibitor or agonist
- No other systemic or local anticancer medications
Contacts and Locations
Show 224 Study Locations| Principal Investigator: | Frank Hodi | Eastern Cooperative Oncology Group |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01134614 History of Changes |
| Other Study ID Numbers: | NCI-2011-02039, E1608, U10CA021115, CDR0000671238 |
| Study First Received: | April 27, 2010 |
| Last Updated: | June 12, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue |
Nevi and Melanomas Antibodies, Monoclonal Cytotoxic T-lymphocyte antigen 4 Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Immunosuppressive Agents |
ClinicalTrials.gov processed this record on June 18, 2013