A Multi-center, Randomized, Double-Blind, Two-Arm, Phase III Study in Patients With Untreated Stage III (Unresectable) or IV Melanoma Receiving Dacarbazine Plus 10 mg/kg Ipilimumab (MDX-010) vs. Dacarbazine With Placebo
Overview
- Phase
- Phase 3
- Intervention
- Ipilimumab
- Conditions
- Melanoma
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 681
- Locations
- 33
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this clinical research study is to examine the safety and effectiveness (how well the drug works) of two different treatments for patients with melanoma. One treatment is an investigational compound (a drug that is not currently approved by the United States Food and Drug Administration [FDA]), know as Ipilimumab (also known as MDX-010 or BMS-734016) together with an approved chemotherapy drug called Dacarbazine
Detailed Description
For the extension phase: Allocation: single arm study; Masking: open label; Intervention Model: Single Group
Investigators
Eligibility Criteria
Inclusion Criteria
- •Informed Consent
- •Measurable Disease
- •Eastern Cooperative Oncology Group (ECOG) 0 or 1
- •Lab / imaging requirements
- •Neg for Human Immunodeficiency Virus (HIV), Hepatitis B (HepB), C
- •Men and Women \> 18 years (16 were allowable)
- •Prior therapy restriction (adjuvant only)
- •Pregnant / nursing
- •Inadequate contraception
- •Brain metastasis
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A: Ipilimumab and Dacarbazine
In Maintenance phase: Ipilimumab will be continued. Dacarbazine was given up to Week 22 and is not given in the Maintenance phase
Intervention: Ipilimumab
Arm A: Ipilimumab and Dacarbazine
In Maintenance phase: Ipilimumab will be continued. Dacarbazine was given up to Week 22 and is not given in the Maintenance phase
Intervention: Dacarbazine
Arm B: Placebo and Dacarbazine
Intervention: Placebo
Arm B: Placebo and Dacarbazine
Intervention: Dacarbazine
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Date of randomization to 37 months through 5-year follow-up and up to approximately 76 months
OS was defined as the time from the date of randomization until the date of death. Analysis of OS was to be done once 416 deaths had occurred (primary endpoint). However, analysis occurred at 414 deaths (February 7, 2011), due to operational timing of the study. Median number of months of OS and associated confidence interval calculated using the method of Brookmeyer and Crowley.
Secondary Outcomes
- Disease Control Rate (DCR)(First dose to last tumor assessment prior to subsequent therapy at data cutoff for Primary Endpoint (approximately 5 years))
- Median Number of Months of Progression-free Survival (PFS)(Randomization to date of progression or death to approximately 5 years)
- Survival Rate at 1 Year, 18 Months, 2 Years, and 3 Years(Date of randomization to 3 years following randomization)
- Progression-free Survival (PFS) Rate Truncated at Week 12(Day 78)
- Duration of Stable Disease (SD): Randomized Participants With Stable Disease(Week 12 to date of disease progression or death up to data cutoff for primary endpoint (approximately 5 years))
- Best Overall Response Rate (BORR)(First dose to last tumor assessment at data cutoff for primary endpoint (approximately 5 years))
- Duration of Response (DOR): Randomized Participants With Response of Complete Response (CR) or Partial Response (PR)(Day of CR or PR to day of PD or death up to data cutoff for primary endpoint (approximately 5 years))
- Percentage of Participants With Brain Metastasis-Free Survival at Time of Data Cutoff(Date of randomization up to data cutoff for primary endpoint (approximately 5 years))
- Time to Response: All Randomized Participants With Response to Treatment(First dose to date of BOR up to data cutoff for primary endpoint (approximately 5 years))
- Number of Participants With Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Hypersensitivity, Immune-related AEs/SAEs, and Inflammatory AEs/SAEs(Week 1 (First Dose) to 70 days after last dose of study up to data cutoff for primary endpoint (approximately 5 years))
- Number of Participants With Grade 2-3 and Grade 3-4 Immune-related Adverse Events (irAEs) With Resolution Resolved(Week 1 (first dose) to 70 days after last dose up to data cutoff for primary endpoint (approximately 5 years))
- Time to Resolution of Grade 2-3, Grade 3-4 Immune-related Adverse Events (irAEs)(Week 1 (first dose) to 70 days after last dose up to database lock for primary endpoint (approximately 5 years))