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
This randomized phase II/III trial studies the side effects and best dose 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. Monoclonal antibodies, such as ipilimumab and nivolumab, may kill tumor cells by blocking blood flow to the tumor, by stimulating white blood cells to kill the tumor cells, or by attacking specific tumor cells and stop them from growing or kill them. 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.
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.
|
Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1;
|
|
Patients must have known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational status of tumor, wild-type (WT) or mutated, prior to randomization;
|
|
Women must not be pregnant or breast-feeding, all females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy, a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months);
|
|
Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for at least one week prior to the start of the research study, and continuing for up to 5 months for women of childbearing potential and 7 months for sexually active males after the last dose of the study drugs;
|
|
Patients must have unresectable stage III or stage IV melanoma. Patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive;
|
|
Patients must have measurable disease per RECIST 1.1 criteria, all sites of disease must be evaluated within 4 weeks prior to randomization;
|
|
Contact Study coordinator for more inclusion criteria;
|
|
|
-
Antineoplastic Agents, Immunological
|
|
|
|
|
|
|
|
|
|
|
-
Neoplasms by Histologic Type
|
|
|
-
Neoplasms, Germ Cell and Embryonal
|
|
|
|
|
|
|
|
|
|
|
-
Physiological Effects of Drugs
|
|
|
|
|
|
|
|
|