Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
Condition: Advanced Melanoma; Metastatic Melanoma; Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Unresectable Melanoma
MeSH terms: Melanoma; Skin Neoplasms
Intervention: Ipilimumab; Sargramostim
Intervention description: Given IV; Given SC
Intervention MeSH terms: Ipilimumab; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 245.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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 (unresectable). 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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All sites of disease must be evaluated within 4 weeks prior to randomization; patients
             must have measurable disease as defined by Response Evaluation Criteria in Solid
             Tumors (RECIST)

          -  No more than one prior systemic therapeutic regimen for unresectable stage III or
             stage IV melanoma; this includes chemotherapy, biologic therapy, biochemotherapy, or
             investigational treatment; this does not include any therapies given in the adjuvant
             setting

          -  Histologic diagnosis of metastatic melanoma; for unknown primary disease, diagnosis of
             metastatic disease by cytology fine needle aspiration (FNA) is not acceptable

          -  Women must not be pregnant or breast-feeding due to unknown effects of ipilimumab and
             GM-CSF on the unborn fetus; all women of childbearing potential must have a blood test
             within 72 hours prior to randomization to rule out pregnancy; women of childbearing
             potential and sexually active males must be strongly advised to use an accepted and
             effective method of contraception; women of childbearing potential (WOCBP) must be
             using an adequate method of contraception to avoid pregnancy throughout the study and
             for up to 12 weeks after the last dose of investigational product, in such a manner
             that the risk of pregnancy is minimized; sexually mature females who have not
             undergone a hysterectomy or who have not been postmenopausal naturally for at least 24
             consecutive months (i.e., who have had menses at some time in the preceding 24
             consecutive months) are considered to be of childbearing potential; women who are
             using oral contraceptives, other hormonal contraceptives (vaginal products, skin
             patches, or implanted or injectable products), or mechanical products such as an
             intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent
             pregnancy, or are practicing abstinence or where their partner is sterile (e.g.,
             vasectomy) should be considered to be of childbearing potential

          -  White blood cells (WBC) >= 2000/uL (obtained =< 4 weeks prior to randomization)

          -  Absolute neutrophil count (ANC) >= 1500/mcL (obtained =< 4 weeks prior to
             randomization)

          -  Platelets >= 100,000/mcL (obtained =< 4 weeks prior to randomization)

          -  Hemoglobin >= 8 g/dL (obtained =< 4 weeks prior to randomization)

          -  Creatinine =< 3.0 x upper limit of normal (ULN) (obtained =< 4 weeks prior to
             randomization)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
             (obtained =< 4 weeks prior to randomization)

          -  Bilirubin =< 3.0 x ULN, (except patients with Gilbert's syndrome, who must have a
             total bilirubin less than 3.0 mg/dL) (obtained =< 4 weeks prior to randomization)

          -  No concomitant therapy with any of the following: interleukin (IL) 2, interferon, or
             other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive
             agents; other investigation therapies; or chronic use of systemic corticosteroids;
             must have been discontinued >= 4 weeks

          -  No infection with human immunodeficiency virus (HIV); due to the mechanism of action
             of ipilimumab and GM-CSF, activity and side effects in an immune compromised patient
             are unknown

          -  No active infection with hepatitis B

          -  No active or chronic infection with hepatitis C

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

        Exclusion Criteria:

          -  Patients with any history of central nervous system (CNS) metastases are excluded

          -  Patients are excluded if they have a history of any other malignancy from which the
             patient has been disease-free for less than 2 years, with the exception of adequately
             treated and cured basal or squamous cell skin cancer, superficial bladder cancer or
             carcinoma in situ of the cervix

          -  Patients are excluded if they have a history of any autoimmune disease; patients with
             a history of autoimmune thyroiditis are eligible if their current thyroid disorder is
             treated and stable with replacement or other medical therapy

          -  Patients are excluded for any underlying medical or psychiatric condition, which 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

          -  Patients are excluded for receiving any non-oncology vaccine therapy used for
             prevention of infectious diseases for up to four weeks (28 days) prior to or after any
             dose of ipilimumab

          -  Patients are excluded if they have a history of prior treatment with ipilimumab or
             prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte antigen 4
             (CTLA-4) inhibitor or agonist

          -  Any concurrent medical condition requiring the use of systemic steroids is not
             permitted (the use of inhaled or topical steroids is permitted)