Phase 3 Trial in Subjects With Metastatic Melanoma Comparing 3 mg/kg Ipilimumab Versus 10 mg/kg Ipilimumab
- Conditions
- Melanoma
- Interventions
- Biological: Ipilimumab
- Registration Number
- NCT01515189
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine whether giving Ipilimumab at a dose of 10mg/kg will extend the lives of subjects with unresectable or metastatic melanoma more than giving Ipilimumab at a dose of 3 mg/kg
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 831
- Unresectable Stage III or Stage IV melanoma
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Brain metastases with symptoms or requiring treatment
- History of autoimmune disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Ipilimumab (3 mg/kg) Ipilimumab Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses; option for Re-induction, until disease progression or unacceptable toxicity Arm 2: Ipilimumab (10 mg/kg) Ipilimumab Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses; option for Re-induction, until disease progression or unacceptable toxicity
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Approximately 48 months (assessed up to February 2016) OS is defined for each participant as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Median and associated 2-sided 95% confidence intervals were calculated using the method of Brookmeyer and Crowley.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) by mWHO Criteria From date of randomization until 540 death events occurred (approximately 48 months) PFS was defined as the time between randomization date and the date of progression or death, whichever occurred first. A participant who died without reported prior progression was considered to have progressed on the date of death. For a participant who underwent resection post randomization, PFS was censored on last tumor assessment date prior to resection. For those who remained alive and had not progressed, PFS was censored on last evaluable tumor assessment date. Participants who had not died and had no recorded post-baseline tumor assessment were censored at the day of randomization. For participants who had Progressive Disease (PD) prior to Week 12 and a subsequent assessment of Stable Disease (SD), Partial Response (PR), or Complete Response (CR), the date of PD following response was used in the analysis of PFS; otherwise these participants were censored on the date of their last tumor assessment. Median and 2-sided 95% CIs were calculated with Brookmeyer Crowley method.
Duration of Response (DOR) by mWHO Criteria From date of randomization until 540 death events occurred (approximately 48 months) Duration of response for participants whose BOR was CR or PR was defined as the time between the date measurement criteria were first met for overall response of PR or CR (whichever status was recorded first) and the date of disease progression or death (whichever occurred first). For participants who underwent tumor resection following response but prior to disease progression, duration of response was censored on the date of last evaluable tumor assessment prior to resection. For participants who had BOR of SD, PR or CR at Week 12, or a confirmed response of PR or CR before Week 12, the date of PD following thereafter (where available) was used in the analysis of duration of response. For those participants who remained alive and had not progressed following response, duration of response was censored on the date of last evaluable tumor assessment. Median and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer Crowley method.
Duration of Stable Disease by mWHO Criteria From date of randomization until 540 death events occurred (approximately 48 months) Duration of stable disease was defined for participants whose BOR was SD as the time between when SD was first documented and the date of PD or death (whichever occurred first). For a participant who underwent tumor resection following Week 12 but prior to disease progression, duration of stable disease was censored on the date of the last evaluable tumor assessment prior to resection. For participants who had BOR of SD at Week 12, the date of PD following thereafter (where available) was used in the analysis of duration of stable disease. For participants with BOR of SD who had not subsequently progressed and who remained alive, duration of stable disease was censored on the date of last evaluable tumor assessment. Median and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer and Crowley method.
Best Overall Response Rate (BORR) by mWHO Criteria From date of randomization until 540 death events occurred (approximately 48 months) BORR by treatment arm was defined as the total number of randomized participants in the arm whose BOR is CR or PR, divided by the total number of randomized participants in the arm. Any participant who was unevaluable for BOR, e.g. on account of missing or "not evaluable" assessments, was included in the denominator of the calculation (i.e. was considered a non-responder with respect to the BORR endpoint). 95% 2-sided exact confidence intervals were computed using the method of Clopper and Pearson.
Disease Control Rate (DCR) by mWHO Criteria From date of randomization until 540 death events occurred (approximately 48 months) DCR by treatment arm was defined as the total number of randomized participants in the arm whose BOR is CR, PR or SD, divided by the total number of randomized participants in the arm. Any participant who was unevaluable for Disease Control (DC), (e.g. on account of missing or "not evaluable" assessments), was included in the denominator of the calculation (i.e. was considered a non-responder with respect to the DCR endpoint). 95% 2-sided exact confidence intervals were computed using the Clopper and Pearson method.
Rate of Overall Survival Approximately 66 months OS is defined for each participant as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Survival rates were calculated based on Kaplan-Meier estimation with log-log transformed confidence intervals. The survival rate at x year(s) is defined as the probability that a subject is alive at x year(s) following randomization.
Overall Survival of Participants With Brain Metastases at Baseline From date of randomization until 540 death events occurred (approximately 48 months) OS for each participant with brain metastases at baseline was measured as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Median OS, and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer and Crowley method.
Trial Locations
- Locations (14)
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
The Angeles Clinic And Research Institute
🇺🇸Los Angeles, California, United States
University Of California Los Angeles
🇺🇸Los Angeles, California, United States
Oncology Specialists, S.C.
🇺🇸Park Ridge, Illinois, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Fundacion Cidea
🇦🇷Buenos Aires, Argentina
Instituto Valenciano De Oncologia
🇪🇸Valencia, Spain
Baptist Cancer Institute
🇺🇸Jacksonville, Florida, United States
Orlando Health, Inc
🇺🇸Orlando, Florida, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
St. Luke's Cancer Center - Anderson Campus
🇺🇸Easton, Pennsylvania, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Local Institution
🇬🇧Swansea, United Kingdom