Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01134614
First received: April 27, 2010
Last updated: March 23, 2015
Last verified: March 2015

April 27, 2010
March 23, 2015
December 2010
February 2013   (final data collection date for primary outcome measure)
Overall Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years ] [ Designated as safety issue: No ]
Overall survival is defined as the time from randomization to death from any cause.
Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01134614 on ClinicalTrials.gov Archive Site
  • Progression-free Survival (PFS) [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time from randomization to disease progression or death, whichever occurs first. Response and disease progression will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Disease progression is defined as >= 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions is also considered progression.
  • Proportion of Patients With Objective Response [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years ] [ Designated as safety issue: No ]
    Objective response was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial response (PR)= At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. To be assigned a status of partial response, changes in tumor measurements must be confirmed by a repeat assessment performed no less than four weeks after the criteria for response is met. Objective response = CR + PR.
  • Progression-free survival [ Designated as safety issue: No ]
  • Response rate [ Designated as safety issue: No ]
  • Safety and tolerability [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery
A Phase II Trial of GM-CSF Protein Plus Ipilimumab in Patients With Advanced Melanoma

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Melanoma
  • Stage III Melanoma
  • Stage IV Melanoma
  • Biological: ipilimumab
    Given IV
    Other Names:
    • Anti-CTLA-4 monoclonal antibody
    • MDX-010
  • Biological: sargramostim
    Given SC
    Other Names:
    • Granulocyte-macrophage colony stimulating factor (GM-CSF)
    • rHu GM-CSF
    • Leukine
  • Experimental: Arm A (ipilimumab and sargramostim)
    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.
    Interventions:
    • Biological: ipilimumab
    • Biological: sargramostim
  • Experimental: Arm B (ipilimumab)
    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.
    Intervention: Biological: ipilimumab
Hodi FS, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, Leming P, Puzanov I, Shin D, Kirkwood JM. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014 Nov 5;312(17):1744-53. doi: 10.1001/jama.2014.13943.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
245
August 2016
February 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01134614
NCI-2011-02039, NCI-2011-02039, E1608, U10CA021115
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Study Chair: Frank Hodi, MD Dana-Farber Cancer Institute
National Cancer Institute (NCI)
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP