A Randomized Phase II Trial of Ipilimumab With or Without Bevacizumab in Patients With Unresectable Stage III or Stage IV Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Ipilimumab
- Conditions
- Stage IIIC Cutaneous Melanoma AJCC v7
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 169
- Locations
- 481
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
This randomized phase II trial studies how well ipilimumab with or without bevacizumab works in treating patients with stage III-IV melanoma that cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab and bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVES: I. To compare overall survival for patients receiving ipilimumab plus bevacizumab versus ipilimumab alone. SECONDARY OBJECTIVES: I. To evaluate the progression free survival, response rate and safety in patients receiving ipilimumab plus bevacizumab versus ipilimumab alone. II. To evaluate the utility of immune related response criteria (irRC) in patients receiving ipilimumab plus bevacizumab versus ipilimumab alone. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: INDUCTION THERAPY: Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab IV over 90 minutes on day 1. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. ARM B: INDUCTION THERAPY: Patients receive ipilimumab IV over 90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab IV over 90 minutes on day 1. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1
- •Untreated or previously received one treatment regimen for measurable unresectable stage III or stage IV melanoma (American Joint Committee on Cancer \[AJCC\] 2010) (for BRAF wild-type, and regardless of human leukocyte antigen \[HLA\] type); untreated or previously received up to two treatment regimens for measurable unresectable stage III or stage IV melanoma (AJCC 2010) (for BRAF mutant, and regardless of HLA type; if 2 prior regimens, one should be a BRAF inhibitor); this does not include any therapies given in the adjuvant setting
- •Prior treatment (chemotherapy \[chemo\], radiation, hormone, and immune therapies) must be completed \> 4 weeks prior to randomization (\> 6 weeks prior to randomization for nitrosoureas, mitomycin C, and checkpoint inhibitors)
- •Patients who received prior therapy with anthracyclines should have a baseline multigated acquisition scan (MUGA) or echocardiogram (echo) with a normal ejection fraction within 28 days prior to randomization
- •Patients must have recovered from any acute toxicity associated with prior therapy by the start of study treatment
- •Women must not be pregnant or breast-feeding due to the unknown effects on the fetus or infant; 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)
- •All sites of disease must be evaluated within 4 weeks prior to randomization; patients must have measurable disease
- •White blood cell (WBC) \>= 2000/uL (obtained within 4 weeks prior to randomization)
- •Absolute neutrophil count (ANC) \>= 1000/uL (obtained within 4 weeks prior to randomization)
- •Platelets \>= 75 x 10\^3/uL (obtained within 4 weeks prior to randomization)
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A (ipilimumab)
INDUCTION THERAPY: Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab IV over 90 minutes on day 1. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Ipilimumab
Arm B (ipilimumab and bevacizumab)
INDUCTION THERAPY: Patients receive ipilimumab IV over 90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab IV over 90 minutes on day 1. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Arm B (ipilimumab and bevacizumab)
INDUCTION THERAPY: Patients receive ipilimumab IV over 90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab IV over 90 minutes on day 1. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Ipilimumab
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Time from randomization to death from any cause, assessed up to 5 years
OS distributions will be estimated using the Kaplan-Meier method. The distribution of OS will be compared using the stratified log rank test with one-sided overall type I error rate of 0.100 (adjusting for the one interim analysis) and the hazard ratio of OS will be estimated using the stratified Cox proportional hazard model and one-sided 90% repeated confidence interval will be constructed.
Secondary Outcomes
- Incidence of Adverse Events (AE)(Up to 90 days after completion of study treatment, up to 5 years post-registration.)
- Progression-free Survival (PFS)(Time from randomization to disease progression or death (whichever occurs first), assessed up to 5 years)
- Clinical Response Rate(Up to 5 years)
- Immune-related (ir) Responses Rate (Ir-CR+Ir-PR)(Up to 5 years)