Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma

• Overall Survival [ Time Frame: Patient Status is assessed at every visit (Weeks 1, 4, 7, 10, 12, 13, 16, 19, 20, 22, 24 in the Induction Phase, Weeks 24, 30, 36, 42, 48 and every 12 weeks thereafter in the Maintenance Phase, and every 12 weeks in the Follow-up Phase) ] [ Designated as safety issue: No ]
• Extension phase: Survival rates at 3, 4 and 5 years [ Time Frame: Patient Status is assessed at every visit (every 12 weeks in the Extended Dosing Phase and every 24 weeks in the Extended Follow-Up Phase) ] [ Designated as safety issue: No ]

• Progression-free survival [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ] [ Designated as safety issue: No ]
• Disease Control Rate [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ] [ Designated as safety issue: No ]
• Best Overall Response Rate [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ] [ Designated as safety issue: No ]
• Survival rate at one year, eighteen months, and two years [ Time Frame: Patient Status is assessed at every visit (Weeks 1, 4, 7, 10, 12, 13, 16, 19, 20, 22, 24 in the Induction Phase, Weeks 24, 30, 36, 42, 48 and every 12 weeks thereafter in the Maintenance Phase, and every 12 weeks in the Follow-up Phase) ] [ Designated as safety issue: No ]
• Duration of response [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ] [ Designated as safety issue: No ]
• Time to Response [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ] [ Designated as safety issue: No ]
• Safety Profile [ Time Frame: Adverse Events are assessed at every visit (Weeks 1, 4, 7, 10, 12, 13, 16, 19, 20, 22, 24 in the Induction Phase, Weeks 24, 30, 36, 42, 48 and every 12 weeks thereafter in the Maintenance Phase, and every 12 weeks in the Follow-up Phase) ] [ Designated as safety issue: Yes ]
• Health-Related Quality of Life (QoL) [ Time Frame: QoL assessments are performed at Weeks 1, 4, 7, 12, 24, 36, 48, and at the first follow-up phase visit ] [ Designated as safety issue: No ]
• Population Pharmacokinetics (PK) [ Time Frame: PK samples are collected at Weeks 1, 7, 7 to 8, 8 to 9, and 10 ] [ Designated as safety issue: No ]
• Extension phase: Safety profile of Ipilimumab for patients in the Extension Phase [ Time Frame: Safety will be assessed every 12 weeks in the Extended Dosing Phase and every 24 weeks in the Extended Follow-Up Phase ] [ Designated as safety issue: No ]
  Incidence of adverse events and their severity

• Overall Survival
• Survival at 1 year
• PFS at Week 12
• Best Overall Response (BOR) and Duration
• Disease control rate
• Time to BOR
• Safety profile
• Health-Related QoL
• Population PK

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

For the extension phase:

Allocation: single arm study; Masking: open label; Intervention Model: Single Group

• Drug: Ipilimumab

  Intravenous solution; intravenous; 10mg/kg; one dose every 3 wks for 10wks then one dose every 12 wks starting at Wk24, until disease progression, unacceptable toxicity or withdrawal of consent

  In Extension phase: Only Ipilimumab: 10mg/kg, every 12 wks will be continued until disease progression

  Other Names:

  • MDX-010
  • BMS-734016
• Drug: Placebo
  Intravenous solution; intravenous; 0 mg; one dose every 3 wks for 10 wks then one dose every 12w ks starting at Wk24; until disease progression, unacceptable toxicity or withdrawal of consent
• Drug: Dacarbazine
  Intravenous solution; intravenous; 850 mg/m2; one dose every 3 wks for 22 wks, until disease progression, unacceptable toxicity or withdrawal of consent

• Experimental: Arm A: Ipilimumab and Dacarbazine
  In Extension phase: Ipilimumab will be continued. Dacarbazine was given up to Week 22 and is not given in the Extension phase
  Interventions:

  • Drug: Ipilimumab
  • Drug: Dacarbazine
• Active Comparator: Arm B: Placebo and Dacarbazine
  Interventions:

  • Drug: Placebo
  • Drug: Dacarbazine

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)

Exclusion:

• Pregnant / nursing
• Inadequate contraception
• Brain metastasis
• Primary ocular or mucosal melanoma