Drug-Drug Interaction - 3 Arm - Carboplatin/Paclitaxel, Dacarbazine

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00796991
• Collaborator: Medarex (Industry)
• Enrollment: 72
• Locations: 4
• Arms: 3
• Duration (Months): 44
• Patients Per Site: 18
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to learn the pharmacokinetics of Ipilimumab when combined with Paclitaxel/Carboplatin or Dacarbazine

Condition or Disease	Intervention/Treatment	Phase
Advanced Melanoma	Drug: Ipilimumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Dacarbazine	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Parallel, 3-arm Study to Characterize the Effect of Ipilimumab + Chemotherapy in Patients With Untreated Advanced Melanoma
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A	Drug: Ipilimumab; Solution, intravenous, 10mg/kg, every 3 weeks in the induction phase, up to 4 doses in the induction phase, 48 weeks; Other Names: BMS-734016 MDX-010 ; Drug: Carboplatin; Solution, intravenous, Area Under the Concentration Time Curve=6, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks; Other Names: BMY-26575 PARAPLATIN ; Drug: Paclitaxel; Solution, intravenous, 175 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks; Other Names: TAXOL BMS-181339
Active Comparator: Arm B	Drug: Ipilimumab; Solution, intravenous, 10mg/kg, every 3 weeks in the induction phase, up to 4 doses in the induction phase, 48 weeks; Other Names: BMS-734016 MDX-010 ; Drug: Dacarbazine; Solution, intravenous, 850 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks
Active Comparator: Arm C	Drug: Ipilimumab; Solution, intravenous, 10mg/kg, every 3 weeks in the induction phase, up to 4 doses in the induction phase, 48 weeks; Other Names: BMS-734016 MDX-010

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population [Day 1 (0 h) to Day 43]

   Cmax=micrograms per milliliter (µg/mL): drug concentration versus time for ipilimumab (Day 43) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma by Enzyme-linked Immunosorbent Assay (ELISA); lower level of quantitation (LLOQ)=0.8 µg/mL; upper limit of quantitation (ULOQ)=25.6 µg/mL; Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; from Day 162 on every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined using liquid chromatography tandem mass spectrometry (LC/MS/MS) detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography atmospheric pressure ionization (API) tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.

2. Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population [Day 1 (0 h) to Day 43]

   AUC=micrograms*hour(h) per mL (µg*h/mL): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.

Secondary Outcome Measures

1. Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population [Day 1 (0 h) to Day 43]

   Tmax reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose..

2. Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population [Day 1 (0 h) to Day 43]

   T(HALF) reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.

3. Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population [Day 1 (0 h) to Day 43]

   CLT reported in milliliters/hour (mL/h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose..

4. Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population [Day 1 (0 h) to Day 43]

   Vss reported in liters(L): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.

5. Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants [Day 1 to Week 48]

   Assessments for antitumor activity by physical exam and routine anatomic imaging were at Week 12 and confirmatory imaging at Weeks 16, 20, and 24. Participants with resected index or new lesions were considered progressed in their disease. Complete Response (CR): Complete disappearance of all index lesions; Partial Response (PR): Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions, in the absence of Complete Response; Stable Disease (SD): Does not meet criteria for complete or partial response, in the absence of progressive disease. Participants with PR or CR that was not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions; Progressive Disease: At least 25% increase in the sum of products of all index lesions and/or the appearance of any new lesion(s). Unknown=the participants overall response was not known.

6. Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants [Day 1 to Week 48]

   Assessments: Weeks 12, 16, 20, and 24. Participants with resected index or new lesions considered progressed in their disease. The immune-related (ir) response criteria (irRC) represents further modifications of mWHO criteria reflecting clinical experience with ipilimumab in which objective and durable responses (as per mWHO) were observed in participants following progression and without intervening alternative anti-cancer therapy. Immune-related (ir)Complete Response (irCR): Complete disappearance of all index lesions; ir Partial Response (irPR): Decrease, relative to baseline, of 50% or greater in sum of products of the two largest perpendicular diameters of all index and all new measurable lesions, in the absence of irCR; ir Stable Disease (irSD): Does not meet criteria for irCR or irPR, in the absence of progressive disease (PD); ir PD: At least 25% increase in Tumor Burden compared to sum of product diameters (SPD) at nadir. ir Unknown=participants overall response not known.

7. Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants [Day 1 to Week 48]

   Number of participants with an objective response to treatment excluded participants with a best overall response (BOR) of Stable Disease (SD). Disease control is non-progression of disease while on treatment. A participant was considered to have achieved disease control if he/she had a BOR of CR, PR, or SD in the absence of resected index lesions or new lesions while the participant was considered to have an objective response to treatment in he/she had a BOR of CR or PR in the absence of resected index lesions or new lesions.

8. Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population [Day 1 to Week 48]

   Adverse events (AEs) and Serious AEs (SAEs) were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events version 3.0. Week 48 database lock was 27 July 2010.

9. Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population [Day to Week 12]

   Absolute lymphocyte counts were obtained from routine hematology panels from 28 days prior to the first treatment with any study medication through the end of the Induction-Dosing Period and were reported as number*10^3 cells per micro liter (x10^3 c/µL).

10. Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population [Day 1 to Week 48]

    Blood pressure was obtained while the participant was sitting down and was measured in millimeters of mercury (mmHg). During the induction phase blood pressure was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Orthostatic blood pressure was to be measured when clinically indicated (for example, participant was experiencing lightheadedness, dizziness, syncope). Blood pressures were recorded at Weeks 1, 4, 7, 10,13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.

11. Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population [Day 1 to Week 48]

    Pulse rate was obtained while the participant was sitting down and measured in beats per minute (bpm). During the induction phase pulse rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Pulse rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.

12. Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population [Day 1 to Week 48]

    Respiration rate was obtained while the participant was sitting down and measured in breaths per minute (bpm). During the induction phase respiration rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Respiration rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.

13. Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population [Day 1 to Week 48]

    Temperature was obtained while the participant was sitting down and was measured in degrees Fahrenheit (F). During the induction phase this vital sign was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Temperature was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.

14. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population [Day 1 to Week 48]

    Hemoglobin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 10.0 - less than (<) lower limit of normal (LLN); GRADE (2): 8.0 - < 10.0; GRADE (3): 6.5 - < 8.0; GRADE (4): < 6.5

15. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population [Day 1 to Week 48]

    Leukocytes are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN; GRADE (2): 2.0 - < 3.0; GRADE (3): 1.0 - < 2.0; GRADE (4): < 1.0.

16. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population [Day 1 to Week 48]

    Lymphocytes (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 0.8 - < 1.5; GRADE (2): 0.5 - < 0.8; GRADE (3): 0.2 - < 0.5; GRADE (4): < 0.2

17. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population [Day 1 to Week 48]

    Neutrophils (absolute) are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5

18. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population [Day 1 to Week 48]

    Neutrophils plus bands (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5.

19. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population [Day 1 to Week 48]

    Platelets were measured as *10^9 cells per liter (c/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 75.0 - < LLN; GRADE (2): 50.0 - < 75.0; GRADE (3): 25.0 - < 50.0; GRADE (4): < 25.0.

20. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population [Day 1 to Week 48]

    ALT was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN.

21. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population [Day 1 to Week 48]

    AST was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN.

22. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population [Day 1 to Week 48]

    Albumin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): < LLN - 3.0; GRADE (2): < 3.0 - 2.0; GRADE (3): < 2.0 g/dL.

23. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population [Day 1 to Week 48]

    Alkaline Phosphatase was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN.

24. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population [Day 1 to Week 48]

    Total Bilirubin was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 3.0 * ULN; GRADE (3): > 3.0 - 10.0 * ULN; GRADE (4): > 10.0 * ULN.

25. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population [Day 1 to Week 48]

    Serum potassium was measured as milliequivalents per liter (mEq/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN OR > ULN - 5.5;; GRADE (2): > 5.5 - 6.0; GRADE (3): 2.5 - < 3.0 > 6.0 - 7.0; GRADE (4): < 2.5 mEq/L.

26. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population [Day 1 to Week 48]

    Amylase was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 * ULN.

27. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population [Day 1 to Week 48]

    Total Calcium was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 8.0 - < LLN OR > ULN - 11.5; GRADE (2): 7.0 - < 8.0 > 11.5 - 12.5; GRADE (3): 6.0 - < 7.0 > 12.5 - 13.5; GRADE (4): < 6.0 > 13.5 mg/dL.

28. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population [Day 1 to Week 48]

    Total Lipase (as measured with a turbidimetric assay) was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * ULN; GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 X ULN.

29. Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population [Day 1 to Week 48]

    Uric acid was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 * ULN - 10.0; GRADE (4): > 10.0 mg/dL.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologic diagnosis of advanced malignant melanoma

• Eastern Cooperative Oncology Group (ECOG) performances status 0-1

• Measurable/evaluable disease as per modified World Health Organization (mWHO) criteria

Exclusion Criteria:

• Evidence of active brain metastases

• Prior treatment with anti-cytotoxic lymphocyte antigen 4 (CTLA-4) or anti-CD137 (type of tumor necrosis factor) antibody

• Total Bilirubin greater than (>) 1.5 * upper limit of normal (ULN) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 * upper limit of normal (ULN)

• Prior Autoimmune disease

• Use of immunosuppressing therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Angeles Clinic & Research Inst.	Los Angeles	California	United States	90025
2	H Lee Moffit Cancer Cnt And Res Inst	Tampa	Florida	United States	33612
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
4	Blumenthal Cancer Center, Carolinas Medical Center	Charlotte	North Carolina	United States	28204

Sponsors and Collaborators

• Bristol-Myers Squibb
• Medarex

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00796991
• Other Study ID Numbers: CA184-078
• First Posted: Nov 24, 2008
• Last Update Posted: Jan 6, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Bristol-Myers Squibb: Untreated Advanced Melanoma
• Additional relevant MeSH terms: Melanoma; Paclitaxel; Carboplatin; Ipilimumab; Dacarbazine

Study Results

Participant Flow

Recruitment Details	17 February 2009 study initiated; last patient, last visit (LPLV) 30 October 2012.
Pre-assignment Detail	72 enrolled; 59 randomized and treated with study drug. Reasons for non-randomization: 7 no longer met study criteria; 3 withdrew consent; 1 had target lesion <1 cm; 1 had screening magnetic resonance imaging (MRI) showed brain metastases; 1 had adverse event.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Period Title: Overall Study
STARTED	20	19	20
COMPLETED	5	7	6
NOT COMPLETED	15	12	14

Baseline Characteristics

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab	Total
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Total of all reporting groups
Overall Participants	20	19	20	59
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 75%	12 63.2%	12 60%	39 66.1%
>=65 years	5 25%	7 36.8%	8 40%	20 33.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (14)	54 (17)	60 (11)	57 (14)
Sex: Female, Male (Count of Participants)
Female	7 35%	6 31.6%	8 40%	21 35.6%
Male	13 65%	13 68.4%	12 60%	38 64.4%
Region of Enrollment (participants) [Number]
United States	20 100%	19 100%	20 100%	59 100%
Eastern Cooperative Oncology Group (ECOG) (participants) [Number]
0	14 70%	17 89.5%	16 80%	47 79.7%
1	6 30%	1 5.3%	4 20%	11 18.6%
2	0 0%	0 0%	0 0%	0 0%
Not Reported	0 0%	1 5.3%	0 0%	1 1.7%
Number of Target Lesions (Number) [Number]
1 lesion	4 20%	3 15.8%	4 20%	11 18.6%
2 lesions	3 15%	3 15.8%	0 0%	6 10.2%
3 lesions	3 15%	4 21.1%	4 20%	11 18.6%
4 lesions	0 0%	2 10.5%	5 25%	7 11.9%
>=5 lesions	10 50%	7 36.8%	7 35%	24 40.7%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population
Description	Cmax=micrograms per milliliter (µg/mL): drug concentration versus time for ipilimumab (Day 43) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma by Enzyme-linked Immunosorbent Assay (ELISA); lower level of quantitation (LLOQ)=0.8 µg/mL; upper limit of quantitation (ULOQ)=25.6 µg/mL; Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; from Day 162 on every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined using liquid chromatography tandem mass spectrometry (LC/MS/MS) detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography atmospheric pressure ionization (API) tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.
Time Frame	Day 1 (0 h) to Day 43

Outcome Measure Data

Analysis Population Description

N=participants who received study drug and with adequate Pharmacokinetic (PK) profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	12
Cmax of Ipilimumab N=14, 14, 12	234.54 (29)	246.50 (35)	251.05 (34)
Cmax of Paclitaxel (Day 1) N=20, 0, 0	3.35 (23)	NA (NA)	NA (NA)
Cmax of Paclitaxel (Day 43) N=14, 0, 0	3.19 (26)	NA (NA)	NA (NA)
Cmax of Dacarbazine (Day 1) N=0, 19, 0	NA (NA)	18.23 (37)	NA (NA)
Cmax of Dacarbazine (Day 43) N=0, 16, 0	NA (NA)	18.61 (30)	NA (NA)
Cmax of AIC (Day 1) N=0, 19, 0	NA (NA)	3.57 (36)	NA (NA)
Cmax of AIC (Day 43) N=0, 17, 0	NA (NA)	3.98 (40)	NA (NA)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel, Carboplatin, Ipilimumab
	Comments	Estimated effect of ipilimumab on paclitaxel Cmax. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the paclitaxel/carboplatin/ipilimumab combination (Day 43) relative to paclitaxel/carboplatin alone (Day 1)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.963
	Confidence Interval	(2-Sided) 90%; 0.794 to 1.168
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dacarbazine, Ipilimumab
	Comments	Estimated effect of ipilimumab on dacarbazine Cmax. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	1.027
	Confidence Interval	(2-Sided) 90%; 0.848 to 1.243
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dacarbazine, Ipilimumab
	Comments	Estimated effect of ipilimumab on AIC Cmax. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	1.058
	Confidence Interval	(2-Sided) 90%; 0.974 to 1.150
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel, Carboplatin, Ipilimumab, Ipilimumab
	Comments	Estimated effect of paclitaxel/carboplatin on ipilimumab Cmax: linear model was applied to ipilimumab log(Cmax)) data from Week 7 (Day 43) PK measurements in first and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the 3 drug combination relative to ipilimumab alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.934
	Confidence Interval	() 90%; 0.768 to 1.136
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Dacarbazine, Ipilimumab, Ipilimumab
	Comments	Estimated effect of dacarbazine on ipilimumab Cmax: linear model was applied to ipilimumab log(Cmax) data from Week 7 (Day 43) PK measurements in second and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination relative to ipilimumab alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.982
	Confidence Interval	(2-Sided) 90%; 0.798 to 1.208
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
Description	Tmax reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose..
Time Frame	Day 1 (0 h) to Day 43

Outcome Measure Data

Analysis Population Description

N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	12
Tmax of Ipilimumab N=14, 14, 12	1.51	4.00	1.56
Tmax of Paclitaxel (Day 1) N=20, 0, 0	3.00	NA	NA
Tmax of Paclitaxel (Day 43) N=14, 0, 0	3.00	NA	NA
Tmax of Dacarbazine (Day 1) N=0, 18, 0	NA	1.00	NA
Tmax of Dacarbazine (Day 43) N=0, 15, 0	NA	1.00	NA
Tmax of AIC (Day 1) N=0, 19 0	NA	1.00	NA
Tmax of AIC (Day 43) N=0, 16, 0	NA	1.00	NA

3. Secondary Outcome

Title	Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
Description	T(HALF) reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.
Time Frame	Day 1 (0 h) to Day 43

Outcome Measure Data

Analysis Population Description

N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	12
T(HALF) of Ipilimumab N=14, 14, 12	13.93 (7.54)	13.39 (4.51)	15.25 (4.64)
T(HALF) of Paclitaxel (Day 1) N=20, 0, 0	10.26 (1.57)	NA (NA)	NA (NA)
T(HALF) of Paclitaxel (Day 43) N=14, 0, 0	10.41 (2.73)	NA (NA)	NA (NA)
T(HALF) of Dacarbazine (Day 1) N=0, 19, 0	NA (NA)	2.11 (0.87)	NA (NA)
T(HALF) of Dacarbazine (Day 43) N=0, 16, 0	NA (NA)	2.07 (0.85)	NA (NA)
T(HALF) of AIC (Day 1) N=0, 18, 0	NA (NA)	2.24 (0.96)	NA (NA)
T(HALF) of AIC (Day 43) N=0, 16, 0	NA (NA)	2.21 (0.81)	NA (NA)

4. Secondary Outcome

Title	Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
Description	CLT reported in milliliters/hour (mL/h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose..
Time Frame	Day 1 (0 h) to Day 43

Outcome Measure Data

Analysis Population Description

N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	12
CLT of Ipilimumab N=14, 14, 12	11.63 (50)	11.17 (34)	10.23 (44)
CLT of Paclitaxel (Day 1) N=20, 0, 0	27.87 (28)	NA (NA)	NA (NA)
CLT of Paclitaxel (Day 43) N=14, 0, 0	25.44 (26)	NA (NA)	NA (NA)
CLT of Dacarbazine (Day 1) N=0, 19, 0	NA (NA)	34.33 (52)	NA (NA)
CLT of Dacarbazine (Day 43) N=0, 16, 0	NA (NA)	37.09 (49)	NA (NA)
CLT of AIC (Day 1) N=0, 19, 0	NA (NA)	91.67 (28)	NA (NA)
CLT of AIC (Day 43) N=0, 17, 0	NA (NA)	88.75 (37)	NA (NA)

5. Primary Outcome

Title	Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population
Description	AUC=micrograms*hour(h) per mL (µg*h/mL): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.
Time Frame	Day 1 (0 h) to Day 43

Outcome Measure Data

Analysis Population Description

N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	12
AUC(0-21d) of Ipilimumab N=14, 14, 12	46925.36 (36)	49569.06 (25)	54039.79 (28)
AUC(INF) of Paclitaxel (Day 1) N=20, 0, 0	12.37 (24)	NA (NA)	NA (NA)
AUC(INF) of Paclitaxel (Day 43) N=14, 0, 0	13.41 (24)	NA (NA)	NA (NA)
AUC(INF) of Dacarbazine (Day 1) N=0, 19, 0	NA (NA)	47.36 (68)	NA (NA)
AUC(INF) of Dacarbazine (Day 43) N=0, 16, 0	NA (NA)	41.13 (55)	NA (NA)
AUC(INF) of AIC (Day 1) N=0, 18, 0	NA (NA)	17.68 (26)	NA (NA)
AUC(INF) of AIC (Day 43) N=0, 16, 0	NA (NA)	17.38 (36)	NA (NA)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel, Carboplatin, Ipilimumab
	Comments	Estimated effect of ipilimumab on paclitaxel AUC(INF). Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the paclitaxel/carboplatin/ipilimumab combination (Day 43) relative to paclitaxel/carboplatin alone (Day 1).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.068
	Confidence Interval	(2-Sided) 90%; 0.954 to 1.196
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dacarbazine, Ipilimumab
	Comments	Estimated effect of ipilimumab on dacarbazine AUC(INF). Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.912
	Confidence Interval	(2-Sided) 90%; 0.757 to 1.099
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dacarbazine, Ipilimumab
	Comments	Estimated effect of ipilimumab on AUC(INF) for AIC. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.970
	Confidence Interval	(2-Sided) 90%; 0.891 to 1.056
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel, Carboplatin, Ipilimumab, Ipilimumab
	Comments	Estimated effect of paclitaxel/carboplatin on ipilimumab AUC: linear model was applied to ipilimumab log(AUC(0-21d)) data from Week 7 (Day 43) PK measurements in first and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the 3 drug combination relative to ipilimumab alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.934
	Confidence Interval	(2-Sided) 90%; 0.768 to 1.136
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Dacarbazine, Ipilimumab, Ipilimumab
	Comments	Estimated effect of dacarbazine on ipilimumab AUC: linear model was applied to ipilimumab log(AUC(0-21d)) data from Week 7 (Day 43) PK measurements in second and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination relative to ipilimumab alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.982
	Confidence Interval	(2-Sided) 90%; 0.7981 to 1.208
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
Description	Vss reported in liters(L): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.
Time Frame	Day 1 (0 h) to Day 43

Outcome Measure Data

Analysis Population Description

N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	12
Vss of Ipilimumab N=14, 14, 12	5.10 (25)	4.88 (21)	5.05 (29)
Vss of Paclitaxel (Day 43) N=14, 0, 0	205.63 (31)	NA (NA)	NA (NA)
Vss of Dacarbazine (Day 43) N=0, 16, 0	NA (NA)	107.90 (31)	NA (NA)
Vss of AIC (Day 1) N=0, 17, 0	NA (NA)	342.64 (47)	NA (NA)

7. Secondary Outcome

Title	Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants
Description	Assessments for antitumor activity by physical exam and routine anatomic imaging were at Week 12 and confirmatory imaging at Weeks 16, 20, and 24. Participants with resected index or new lesions were considered progressed in their disease. Complete Response (CR): Complete disappearance of all index lesions; Partial Response (PR): Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions, in the absence of Complete Response; Stable Disease (SD): Does not meet criteria for complete or partial response, in the absence of progressive disease. Participants with PR or CR that was not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions; Progressive Disease: At least 25% increase in the sum of products of all index lesions and/or the appearance of any new lesion(s). Unknown=the participants overall response was not known.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Complete Response	1 5%	1 5.3%	0 0%
Partial Response	1 5%	4 21.1%	5 25%
Stable Disease	6 30%	5 26.3%	4 20%
Progressive Disease	9 45%	8 42.1%	8 40%
Unknown	3 15%	1 5.3%	3 15%

8. Secondary Outcome

Title	Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants
Description	Assessments: Weeks 12, 16, 20, and 24. Participants with resected index or new lesions considered progressed in their disease. The immune-related (ir) response criteria (irRC) represents further modifications of mWHO criteria reflecting clinical experience with ipilimumab in which objective and durable responses (as per mWHO) were observed in participants following progression and without intervening alternative anti-cancer therapy. Immune-related (ir)Complete Response (irCR): Complete disappearance of all index lesions; ir Partial Response (irPR): Decrease, relative to baseline, of 50% or greater in sum of products of the two largest perpendicular diameters of all index and all new measurable lesions, in the absence of irCR; ir Stable Disease (irSD): Does not meet criteria for irCR or irPR, in the absence of progressive disease (PD); ir PD: At least 25% increase in Tumor Burden compared to sum of product diameters (SPD) at nadir. ir Unknown=participants overall response not known.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
ir Complete Response	1 5%	1 5.3%	0 0%
ir Partial Response	4 20%	5 26.3%	5 25%
ir Stable Disease	5 25%	5 26.3%	6 30%
ir Progressive Disease	7 35%	7 36.8%	6 30%
ir Unknown	3 15%	1 5.3%	3 15%

9. Secondary Outcome

Title	Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants
Description	Number of participants with an objective response to treatment excluded participants with a best overall response (BOR) of Stable Disease (SD). Disease control is non-progression of disease while on treatment. A participant was considered to have achieved disease control if he/she had a BOR of CR, PR, or SD in the absence of resected index lesions or new lesions while the participant was considered to have an objective response to treatment in he/she had a BOR of CR or PR in the absence of resected index lesions or new lesions.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Randomized Population includes all participants randomized to a treatment arm

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Participants with Objective Response	2 10%	5 26.3%	5 25%
Participants with Disease Control	8 40%	10 52.6%	9 45%

10. Secondary Outcome

Title	Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population
Description	Adverse events (AEs) and Serious AEs (SAEs) were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events version 3.0. Week 48 database lock was 27 July 2010.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Participants with AEs	20 100%	19 100%	20 100%
Participants with SAEs	9 45%	8 42.1%	9 45%
Participants with SAEs Treatment-Related	4 20%	6 31.6%	5 25%
Deaths	12 60%	5 26.3%	7 35%
Deaths Treatment-Related	0 0%	0 0%	0 0%
Participants discontinued due to AE(s)	6 30%	7 36.8%	5 25%

11. Secondary Outcome

Title	Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population
Description	Absolute lymphocyte counts were obtained from routine hematology panels from 28 days prior to the first treatment with any study medication through the end of the Induction-Dosing Period and were reported as number*10^3 cells per micro liter (x10^3 c/µL).
Time Frame	Day to Week 12

Outcome Measure Data

Analysis Population Description

Pharmacodynamic Population: All treated participants with one unambiguous date of first dose; and at least 1 ALC evaluation during the induction-dosing period. For each of these participants, all ALC evaluations from 28 days prior to first dose of any study medication to the end of the induction dosing are included. period.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	29	19	20
Nominal Ipilimumab Induction Dose Number 1	1.19	1.41	1.28
Nominal Ipilimumab Induction Dose Number 2	1.62	2.05	1.56
Nominal Ipilimumab Induction Dose Number 3	1.43	1.96	1.99
Nominal Ipilimumab Induction Dose Number 4	1.42	1.87	1.80
End of Ipilimumab Induction dosing Period	1.67	2.07	1.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel, Carboplatin, Ipilimumab, Dacarbazine, Ipilimumab, Ipilimumab
	Comments	null hypothesis of no mean ALC changes over time in any treatment group. Conditional F-tests were used to test for mean ALC changes over time in each treatment arm and the difference between treatment arms in the pattern of change in ALC over time.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments	p-value was not corrected for multiple testing. F-statistic = 1.86.
	Method	conditional F test
	Comments	15 degrees freedom (DF) in numerator and 335 DF in denominator.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel, Carboplatin, Ipilimumab, Dacarbazine, Ipilimumab, Ipilimumab
	Comments	null hypothesis that the pattern of mean ALC values over time is the same in all treatment groups. Test of overall time-by-treatment interaction used an omnibus conditional F-test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments	P-values were not corrected for multiple testing. F Statistic =0.94
	Method	Omnibus conditional F-test
	Comments	10 Degrees Freedom (DF) in numerator and 335 DF in denominator.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel, Carboplatin, Ipilimumab, Ipilimumab
	Comments	null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments	P-values were not corrected for multiple testing. F Statistic =1.08
	Method	conditional F-test
	Comments	5 Degrees Freedom (DF) in numerator and 335 DF in denominator.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Paclitaxel, Carboplatin, Ipilimumab, Dacarbazine, Ipilimumab
	Comments	null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments	P-values were not corrected for multiple testing. F Statistic =0.39
	Method	conditional F-test
	Comments	5 Degrees Freedom (DF) in numerator and 335 DF in denominator.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Dacarbazine, Ipilimumab, Ipilimumab
	Comments	null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	P-values were not corrected for multiple testing. F Statistic = 1.41
	Method	conditional F-test
	Comments	5 Degrees Freedom (DF) in numerator and 335 DF in denominator.

12. Secondary Outcome

Title	Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population
Description	Blood pressure was obtained while the participant was sitting down and was measured in millimeters of mercury (mmHg). During the induction phase blood pressure was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Orthostatic blood pressure was to be measured when clinically indicated (for example, participant was experiencing lightheadedness, dizziness, syncope). Blood pressures were recorded at Weeks 1, 4, 7, 10,13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug. N=number of treated participants who also had blood pressure value available for analysis.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	1	6	9
Diastolic Blood Pressure at Week 16 (N=1, 6, 9)	10.0 (NA)	6.6 (11.3)	4.9 (13.3)
Diastolic Blood Pressure at Week 48 (N=1, 4, 4)	2.0 (NA)	7.0 (11.3)	8.5 (8.2)
Systolic Blood Pressure at Week 16 (N=1, 6, 9)	22.0 (NA)	2.7 (12.2)	9.7 (14.1)
Systolic Blood Pressure at Week 48 (N=1, 4, 4)	5.0 (NA)	1.0 (17.1)	12.0 (8.6)

13. Secondary Outcome

Title	Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population
Description	Pulse rate was obtained while the participant was sitting down and measured in beats per minute (bpm). During the induction phase pulse rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Pulse rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug. N=number of treated participants who also had a Pulse rate value available for analysis.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	1	6	9
Pulse Rate at Week 16 (N=1, 6, 9)	24.0 (NA)	0.3 (13.9)	-0.7 (15.9)
Pulse Rate at Week 48 (N=1, 4, 4)	-3.0 (NA)	-9.5 (13.6)	7.5 (10.3)

14. Secondary Outcome

Title	Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population
Description	Respiration rate was obtained while the participant was sitting down and measured in breaths per minute (bpm). During the induction phase respiration rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Respiration rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug. N=number of treated participants who also had a Respiration rate value available for analysis.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	1	5	6
Respiration Rate at Week 16 (N=1, 5, 6)	0 (NA)	1.4 (2.4)	-0.8 (2.2)
Respiration Rate at Week 48 (N=1, 3, 3)	-2.0 (NA)	-2.7 (1.2)	-1.3 (1.2)

15. Secondary Outcome

Title	Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population
Description	Temperature was obtained while the participant was sitting down and was measured in degrees Fahrenheit (F). During the induction phase this vital sign was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Temperature was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug. N=number of treated participants who also had a temperature value available for analysis.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Temperature at Week 16 (N=1, 6, 9)	-0.5 (NA)	-0.1 (0.8)	0.2 (0.9)
Temperature at Week 48 (N=1, 4, 4)	0.4 (NA)	0.0 (0.7)	-0.2 (0.7)

16. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population
Description	Hemoglobin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 10.0 - less than (<) lower limit of normal (LLN); GRADE (2): 8.0 - < 10.0; GRADE (3): 6.5 - < 8.0; GRADE (4): < 6.5
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Hemoglobin Grade 0	3 15%	4 21.1%	5 25%
Hemoglobin Grade 1	9 45%	13 68.4%	10 50%
Hemoglobin Grade 2	8 40%	1 5.3%	4 20%
Hemoglobin Grade 3	0 0%	1 5.3%	0 0%
Hemoglobin Not Reported	0 0%	0 0%	1 5%

17. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population
Description	Leukocytes are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN; GRADE (2): 2.0 - < 3.0; GRADE (3): 1.0 - < 2.0; GRADE (4): < 1.0.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Leukocytes Grade 0	8 40%	13 68.4%	17 85%
Leukocytes Grade 1	4 20%	4 21.1%	1 5%
Leukocytes Grade 2	2 10%	2 10.5%	1 5%
Leukocytes Grade 3	5 25%	0 0%	0 0%
Leukocytes Grade 4	1 5%	0 0%	0 0%
Leukocytes Not Reported	0 0%	0 0%	1 5%

18. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population
Description	Lymphocytes (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 0.8 - < 1.5; GRADE (2): 0.5 - < 0.8; GRADE (3): 0.2 - < 0.5; GRADE (4): < 0.2
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Lymphocytes Grade 0	4 20%	5 26.3%	6 30%
Lymphocytes Grade 1	12 60%	13 68.4%	11 55%
Lymphocytes Grade 2	3 15%	1 5.3%	3 15%
Lymphocytes Grade 3	1 5%	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population
Description	Neutrophils (absolute) are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Neutrophils Grade 0	20 100%	18 94.7%	19 95%
Neutrophils Grade 1	0 0%	0 0%	1 5%
Neutrophils Grade 3	0 0%	1 5.3%	0 0%

20. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population
Description	Neutrophils plus bands (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Neutrophils Plus Bands Grade 0	20 100%	18 94.7%	19 95%
Neutrophils Plus Bands Grade 1	0 0%	0 0%	1 5%
Neutrophils Plus Bands Grade 3	0 0%	1 5.3%	0 0%

21. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population
Description	Platelets were measured as *10^9 cells per liter (c/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 75.0 - < LLN; GRADE (2): 50.0 - < 75.0; GRADE (3): 25.0 - < 50.0; GRADE (4): < 25.0.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Platelet Count Grade 0	20 100%	19 100%	18 90%
Platelet Count Grade 1	0 0%	0 0%	2 10%

22. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population
Description	ALT was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
ALT Grade 0	18 90%	18 94.7%	16 80%
ALT Grade 1	2 10%	1 5.3%	3 15%
ALT Grade 2	0 0%	0 0%	1 5%

23. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population
Description	AST was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
AST Grade 0	18 90%	18 94.7%	15 75%
AST Grade 1	2 10%	1 5.3%	4 20%
AST Grade 2	0 0%	0 0%	1 5%

24. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population
Description	Albumin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): < LLN - 3.0; GRADE (2): < 3.0 - 2.0; GRADE (3): < 2.0 g/dL.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Albumin Grade 0	17 85%	14 73.7%	14 70%
Albumin Grade 1	3 15%	5 26.3%	6 30%

25. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population
Description	Alkaline Phosphatase was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Alkaline Phosphatase Grade 0	14 70%	18 94.7%	18 90%
Alkaline Phosphatase Grade 1	6 30%	1 5.3%	0 0%
Alkaline Phosphatase Grade 2	0 0%	0 0%	2 10%

26. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population
Description	Total Bilirubin was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 3.0 * ULN; GRADE (3): > 3.0 - 10.0 * ULN; GRADE (4): > 10.0 * ULN.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Total Bilirubin Grade 0	20 100%	17 89.5%	18 90%
Total Bilirubin Grade 1	0 0%	1 5.3%	2 10%
Total Bilirubin Grade 2	0 0%	1 5.3%	0 0%

27. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population
Description	Serum potassium was measured as milliequivalents per liter (mEq/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN OR > ULN - 5.5;; GRADE (2): > 5.5 - 6.0; GRADE (3): 2.5 - < 3.0 > 6.0 - 7.0; GRADE (4): < 2.5 mEq/L.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Serum Potassium (High) Grade 0	20 100%	17 89.5%	17 85%
Serum Potassium (High) Grade 1	0 0%	2 10.5%	1 5%
Serum Potassium (High) Grade 2	0 0%	0 0%	2 10%

28. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population
Description	Amylase was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 * ULN.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Total Amylase Grade 0	20 100%	19 100%	16 80%
Total Amylase Grade 1	0 0%	0 0%	2 10%
Total Amylase Grade 2	0 0%	0 0%	1 5%
Total Amylase Grade 3	0 0%	0 0%	1 5%

29. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population
Description	Total Calcium was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 8.0 - < LLN OR > ULN - 11.5; GRADE (2): 7.0 - < 8.0 > 11.5 - 12.5; GRADE (3): 6.0 - < 7.0 > 12.5 - 13.5; GRADE (4): < 6.0 > 13.5 mg/dL.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Total Calcium (High) Grade 0	18 90%	19 100%	19 95%
Total Calcium (High) Grade 1	2 10%	0 0%	1 5%

30. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population
Description	Total Lipase (as measured with a turbidimetric assay) was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * ULN; GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 X ULN.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Total Lipase Grade 0	12 60%	6 31.6%	4 20%
Total Lipase Grade 1	1 5%	0 0%	0 0%
Total Lipase Grade 4	0 0%	0 0%	1 5%
Total Lipase Not Reported	7 35%	13 68.4%	15 75%

31. Secondary Outcome

Title	Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population
Description	Uric acid was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 * ULN - 10.0; GRADE (4): > 10.0 mg/dL.
Time Frame	Day 1 to Week 48

Outcome Measure Data

Analysis Population Description

Treated participants received at least one dose of a study drug.

Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab	Dacarbazine, Ipilimumab	Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.	Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
Measure Participants	20	19	20
Uric Acid Grade 0	20 100%	19 100%	17 85%
Uric Acid Grade 1	0 0%	1 5.3%	3 15%

Adverse Events

Time Frame	Day 1 up to last patient last visit (LPLV) 30 October 2012
Adverse Event Reporting Description	Participants continue in the study until disease progression, toxicities requiring discontinuation, withdrawal of consent, or study closure.
Arm/Group Title	Paclitaxel, Carboplatin, Ipilimumab		Dacarbazine, Ipilimumab		Ipilimumab
Arm/Group Description	Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.		Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.		Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure.
All Cause Mortality
	Paclitaxel, Carboplatin, Ipilimumab		Dacarbazine, Ipilimumab		Ipilimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Paclitaxel, Carboplatin, Ipilimumab		Dacarbazine, Ipilimumab		Ipilimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/20 (60%)		10/19 (52.6%)		14/20 (70%)
Blood and lymphatic system disorders
Febrile neutropenia	2/20 (10%)		0/19 (0%)		0/20 (0%)
Pancytopenia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Cardiac disorders
Supraventricular tachycardia	1/20 (5%)		0/19 (0%)		1/20 (5%)
Atrial fibrillation	2/20 (10%)		0/19 (0%)		1/20 (5%)
Endocrine disorders
Hypopituitarism	0/20 (0%)		0/19 (0%)		1/20 (5%)
Gastrointestinal disorders
Autoimmune pancreatitis	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Diarrhoea	1/20 (5%)		1/19 (5.3%)		3/20 (15%)
Haematemesis	1/20 (5%)		0/19 (0%)		0/20 (0%)
Nausea	0/20 (0%)		0/19 (0%)		1/20 (5%)
Small intestinal obstruction	0/20 (0%)		0/19 (0%)		1/20 (5%)
Colitis	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Gastrointestinal haemorrhage	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Abdominal pain	0/20 (0%)		4/19 (21.1%)		1/20 (5%)
Vomiting	0/20 (0%)		0/19 (0%)		1/20 (5%)
General disorders
Asthenia	1/20 (5%)		0/19 (0%)		0/20 (0%)
Fatigue	2/20 (10%)		0/19 (0%)		0/20 (0%)
Pyrexia	3/20 (15%)		1/19 (5.3%)		1/20 (5%)
Hepatobiliary disorders
Autoimmune hepatitis	1/20 (5%)		2/19 (10.5%)		0/20 (0%)
Bile duct obstruction	0/20 (0%)		0/19 (0%)		1/20 (5%)
Infections and infestations
Cystitis	1/20 (5%)		0/19 (0%)		0/20 (0%)
Meningitis aseptic	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Sepsis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Bacteraemia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Femur fracture	1/20 (5%)		0/19 (0%)		0/20 (0%)
Radiation necrosis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Seroma	0/20 (0%)		0/19 (0%)		1/20 (5%)
Investigations
Aspartate aminotransferase increased	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Alanine aminotransferase increased	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Failure to thrive	0/20 (0%)		0/19 (0%)		1/20 (5%)
Hypokalaemia	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Dehydration	2/20 (10%)		1/19 (5.3%)		2/20 (10%)
Hypophosphataemia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Decreased appetite	0/20 (0%)		0/19 (0%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/20 (5%)		0/19 (0%)		0/20 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	8/20 (40%)		1/19 (5.3%)		2/20 (10%)
Malignant pleural effusion	1/20 (5%)		0/19 (0%)		0/20 (0%)
Tumour pain	0/20 (0%)		0/19 (0%)		1/20 (5%)
Metastases to skin	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Metastatic malignant melanoma	0/20 (0%)		0/19 (0%)		1/20 (5%)
Metastases to abdominal cavity	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Metastasis	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Nervous system disorders
Convulsion	0/20 (0%)		1/19 (5.3%)		2/20 (10%)
Optic neuritis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Peripheral motor neuropathy	0/20 (0%)		0/19 (0%)		1/20 (5%)
Psychiatric disorders
Mental status changes	0/20 (0%)		0/19 (0%)		2/20 (10%)
Psychotic disorder	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Renal and urinary disorders
Renal failure	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Renal failure acute	0/20 (0%)		0/19 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Hiccups	0/20 (0%)		0/19 (0%)		1/20 (5%)
Pleural effusion	2/20 (10%)		0/19 (0%)		0/20 (0%)
Pulmonary hypertension	1/20 (5%)		0/19 (0%)		0/20 (0%)
Dyspnoea	4/20 (20%)		1/19 (5.3%)		0/20 (0%)
Pulmonary embolism	1/20 (5%)		0/19 (0%)		0/20 (0%)
Skin and subcutaneous tissue disorders
Erythema nodosum	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Rash	1/20 (5%)		0/19 (0%)		0/20 (0%)
Vascular disorders
Hypotension	0/20 (0%)		2/19 (10.5%)		1/20 (5%)
Other (Not Including Serious) Adverse Events
	Paclitaxel, Carboplatin, Ipilimumab		Dacarbazine, Ipilimumab		Ipilimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/20 (100%)		19/19 (100%)		20/20 (100%)
Blood and lymphatic system disorders
Anaemia	0/20 (0%)		2/19 (10.5%)		2/20 (10%)
Leukocytosis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Lymphadenopathy	0/20 (0%)		0/19 (0%)		1/20 (5%)
Neutropenia	0/20 (0%)		2/19 (10.5%)		0/20 (0%)
Lymphopenia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Thrombocytopenia	1/20 (5%)		2/19 (10.5%)		1/20 (5%)
Cardiac disorders
Sinus tachycardia	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Cyanosis	1/20 (5%)		0/19 (0%)		0/20 (0%)
Ear and labyrinth disorders
Auricular perichondritis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Endocrine disorders
Hypopituitarism	1/20 (5%)		0/19 (0%)		1/20 (5%)
Hypothyroidism	0/20 (0%)		2/19 (10.5%)		2/20 (10%)
Hypophysitis	0/20 (0%)		2/19 (10.5%)		5/20 (25%)
Adrenal insufficiency	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Eye disorders
Vision blurred	2/20 (10%)		1/19 (5.3%)		1/20 (5%)
Ocular discomfort	0/20 (0%)		0/19 (0%)		1/20 (5%)
Photophobia	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Visual impairment	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Eye pain	1/20 (5%)		0/19 (0%)		0/20 (0%)
Mydriasis	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Uveitis	1/20 (5%)		1/19 (5.3%)		0/20 (0%)
Dry eye	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Diplopia	1/20 (5%)		0/19 (0%)		0/20 (0%)
Periorbital oedema	0/20 (0%)		0/19 (0%)		1/20 (5%)
Cataract	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Photopsia	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Eye inflammation	0/20 (0%)		0/19 (0%)		1/20 (5%)
Gastrointestinal disorders
Gastritis	1/20 (5%)		0/19 (0%)		0/20 (0%)
Gingival inflammation	0/20 (0%)		0/19 (0%)		1/20 (5%)
Oesophageal pain	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Abdominal discomfort	1/20 (5%)		0/19 (0%)		2/20 (10%)
Abdominal hernia	1/20 (5%)		0/19 (0%)		0/20 (0%)
Flatulence	2/20 (10%)		2/19 (10.5%)		1/20 (5%)
Haemorrhoidal haemorrhage	0/20 (0%)		0/19 (0%)		1/20 (5%)
Oral pain	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Abdominal distension	1/20 (5%)		3/19 (15.8%)		3/20 (15%)
Anal fissure	0/20 (0%)		0/19 (0%)		1/20 (5%)
Oesophagitis	1/20 (5%)		0/19 (0%)		1/20 (5%)
Aphthous stomatitis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Dysphagia	1/20 (5%)		0/19 (0%)		2/20 (10%)
Faecal incontinence	0/20 (0%)		0/19 (0%)		1/20 (5%)
Gastrooesophageal reflux disease	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Stomatitis	1/20 (5%)		1/19 (5.3%)		0/20 (0%)
Haemorrhoids	2/20 (10%)		0/19 (0%)		1/20 (5%)
Abdominal pain upper	1/20 (5%)		4/19 (21.1%)		1/20 (5%)
Diarrhoea	10/20 (50%)		12/19 (63.2%)		12/20 (60%)
Dyspepsia	1/20 (5%)		0/19 (0%)		0/20 (0%)
Nausea	12/20 (60%)		15/19 (78.9%)		7/20 (35%)
Colitis	1/20 (5%)		0/19 (0%)		1/20 (5%)
Constipation	8/20 (40%)		10/19 (52.6%)		7/20 (35%)
Gastrointestinal haemorrhage	1/20 (5%)		0/19 (0%)		0/20 (0%)
Gastrointestinal pain	0/20 (0%)		0/19 (0%)		1/20 (5%)
Mouth haemorrhage	0/20 (0%)		0/19 (0%)		1/20 (5%)
Toothache	0/20 (0%)		0/19 (0%)		1/20 (5%)
Abdominal pain	5/20 (25%)		7/19 (36.8%)		4/20 (20%)
Odynophagia	1/20 (5%)		0/19 (0%)		0/20 (0%)
Vomiting	5/20 (25%)		8/19 (42.1%)		6/20 (30%)
General disorders
Generalised oedema	0/20 (0%)		0/19 (0%)		1/20 (5%)
Chest pain	1/20 (5%)		0/19 (0%)		0/20 (0%)
Discomfort	0/20 (0%)		0/19 (0%)		1/20 (5%)
Fatigue	12/20 (60%)		18/19 (94.7%)		12/20 (60%)
Malaise	0/20 (0%)		2/19 (10.5%)		0/20 (0%)
Spinal pain	0/20 (0%)		0/19 (0%)		1/20 (5%)
Mass	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Mucosal inflammation	2/20 (10%)		0/19 (0%)		1/20 (5%)
Chills	3/20 (15%)		3/19 (15.8%)		2/20 (10%)
Nodule	1/20 (5%)		0/19 (0%)		0/20 (0%)
Pain	3/20 (15%)		1/19 (5.3%)		2/20 (10%)
Early satiety	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Gait disturbance	0/20 (0%)		0/19 (0%)		1/20 (5%)
Infusion site pain	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Mucous membrane disorder	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Oedema peripheral	4/20 (20%)		2/19 (10.5%)		3/20 (15%)
Oedema	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Pyrexia	5/20 (25%)		8/19 (42.1%)		4/20 (20%)
Catheter site discharge	0/20 (0%)		0/19 (0%)		1/20 (5%)
Temperature intolerance	1/20 (5%)		0/19 (0%)		0/20 (0%)
Xerosis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Hepatobiliary disorders
Autoimmune hepatitis	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Hyperbilirubinaemia	1/20 (5%)		0/19 (0%)		0/20 (0%)
Hepatic function abnormal	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Immune system disorders
Autoimmune disorder	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Hypersensitivity	6/20 (30%)		0/19 (0%)		1/20 (5%)
Infections and infestations
Cellulitis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Rocky mountain spotted fever	0/20 (0%)		0/19 (0%)		1/20 (5%)
Bacterial infection	0/20 (0%)		0/19 (0%)		1/20 (5%)
Infection	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Respiratory tract infection	0/20 (0%)		0/19 (0%)		1/20 (5%)
Tooth infection	0/20 (0%)		0/19 (0%)		1/20 (5%)
Urinary tract infection	1/20 (5%)		1/19 (5.3%)		2/20 (10%)
Body tinea	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Pharyngitis	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Staphylococcal infection	0/20 (0%)		0/19 (0%)		1/20 (5%)
Candidiasis	0/20 (0%)		0/19 (0%)		2/20 (10%)
Diverticulitis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Folliculitis	1/20 (5%)		1/19 (5.3%)		0/20 (0%)
Tinea cruris	0/20 (0%)		0/19 (0%)		1/20 (5%)
Tinea pedis	1/20 (5%)		0/19 (0%)		1/20 (5%)
Herpes zoster	0/20 (0%)		0/19 (0%)		1/20 (5%)
Onychomycosis	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Oral herpes	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Salmonellosis	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Sinusitis	0/20 (0%)		2/19 (10.5%)		1/20 (5%)
Upper respiratory tract infection	2/20 (10%)		6/19 (31.6%)		3/20 (15%)
Tooth abscess	1/20 (5%)		0/19 (0%)		0/20 (0%)
Injury, poisoning and procedural complications
Incision site complication	0/20 (0%)		0/19 (0%)		1/20 (5%)
Procedural headache	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Rib fracture	0/20 (0%)		0/19 (0%)		1/20 (5%)
Thermal burn	0/20 (0%)		0/19 (0%)		1/20 (5%)
Laceration	0/20 (0%)		0/19 (0%)		1/20 (5%)
Upper limb fracture	1/20 (5%)		0/19 (0%)		0/20 (0%)
Contusion	1/20 (5%)		0/19 (0%)		0/20 (0%)
Procedural pain	1/20 (5%)		1/19 (5.3%)		0/20 (0%)
Wound complication	0/20 (0%)		0/19 (0%)		1/20 (5%)
Infusion related reaction	1/20 (5%)		0/19 (0%)		0/20 (0%)
Investigations
Blood bilirubin increased	1/20 (5%)		1/19 (5.3%)		0/20 (0%)
Haemoglobin decreased	11/20 (55%)		7/19 (36.8%)		4/20 (20%)
Amylase increased	2/20 (10%)		2/19 (10.5%)		0/20 (0%)
Aspartate aminotransferase increased	5/20 (25%)		10/19 (52.6%)		3/20 (15%)
Blood albumin decreased	1/20 (5%)		0/19 (0%)		1/20 (5%)
Blood corticotrophin decreased	0/20 (0%)		0/19 (0%)		1/20 (5%)
Blood testosterone decreased	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Platelet count decreased	10/20 (50%)		5/19 (26.3%)		1/20 (5%)
Blood creatinine increased	1/20 (5%)		2/19 (10.5%)		2/20 (10%)
Blood phosphorus decreased	0/20 (0%)		0/19 (0%)		1/20 (5%)
Waist circumference increased	0/20 (0%)		0/19 (0%)		1/20 (5%)
Weight increased	1/20 (5%)		0/19 (0%)		1/20 (5%)
White blood cell count decreased	10/20 (50%)		2/19 (10.5%)		1/20 (5%)
Neutrophil count decreased	10/20 (50%)		4/19 (21.1%)		0/20 (0%)
Blood cortisol decreased	0/20 (0%)		0/19 (0%)		1/20 (5%)
Blood alkaline phosphatase increased	6/20 (30%)		5/19 (26.3%)		1/20 (5%)
Weight decreased	2/20 (10%)		4/19 (21.1%)		3/20 (15%)
Alanine aminotransferase increased	5/20 (25%)		10/19 (52.6%)		3/20 (15%)
Blood uric acid increased	0/20 (0%)		0/19 (0%)		1/20 (5%)
Lipase increased	3/20 (15%)		4/19 (21.1%)		1/20 (5%)
Occult blood positive	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Oxygen saturation decreased	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	2/20 (10%)		0/19 (0%)		1/20 (5%)
Hyperuricaemia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Hypoalbuminaemia	7/20 (35%)		2/19 (10.5%)		0/20 (0%)
Hypoglycaemia	1/20 (5%)		0/19 (0%)		1/20 (5%)
Diabetes mellitus	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Hyperkalaemia	5/20 (25%)		0/19 (0%)		0/20 (0%)
Hypermagnesaemia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Gout	0/20 (0%)		0/19 (0%)		2/20 (10%)
Hypokalaemia	3/20 (15%)		2/19 (10.5%)		2/20 (10%)
Hyponatraemia	10/20 (50%)		4/19 (21.1%)		5/20 (25%)
Malnutrition	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Dehydration	0/20 (0%)		0/19 (0%)		2/20 (10%)
Hyperglycaemia	12/20 (60%)		6/19 (31.6%)		5/20 (25%)
Hypocalcaemia	5/20 (25%)		2/19 (10.5%)		1/20 (5%)
Hypophosphataemia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Decreased appetite	6/20 (30%)		8/19 (42.1%)		5/20 (25%)
Hyperalbuminaemia	1/20 (5%)		0/19 (0%)		0/20 (0%)
Hypomagnesaemia	2/20 (10%)		1/19 (5.3%)		0/20 (0%)
Hypovolaemia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Limb discomfort	1/20 (5%)		0/19 (0%)		0/20 (0%)
Myalgia	3/20 (15%)		1/19 (5.3%)		0/20 (0%)
Arthralgia	4/20 (20%)		6/19 (31.6%)		2/20 (10%)
Groin pain	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Muscle spasms	1/20 (5%)		4/19 (21.1%)		1/20 (5%)
Musculoskeletal pain	0/20 (0%)		1/19 (5.3%)		5/20 (25%)
Back pain	2/20 (10%)		4/19 (21.1%)		3/20 (15%)
Musculoskeletal discomfort	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Pain in extremity	3/20 (15%)		3/19 (15.8%)		2/20 (10%)
Muscle haemorrhage	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Neck pain	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Flank pain	0/20 (0%)		0/19 (0%)		2/20 (10%)
Muscular weakness	2/20 (10%)		0/19 (0%)		2/20 (10%)
Intervertebral disc degeneration	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/20 (5%)		0/19 (0%)		0/20 (0%)
Seborrhoeic keratosis	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Lentigo maligna	0/20 (0%)		0/19 (0%)		1/20 (5%)
Malignant ascites	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Angiosarcoma	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Melanocytic naevus	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Squamous cell carcinoma	0/20 (0%)		0/19 (0%)		1/20 (5%)
Nervous system disorders
Migraine	1/20 (5%)		0/19 (0%)		0/20 (0%)
Hypoaesthesia	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Radial nerve palsy	0/20 (0%)		0/19 (0%)		1/20 (5%)
Movement disorder	0/20 (0%)		0/19 (0%)		1/20 (5%)
Sinus headache	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Olfactory nerve disorder	1/20 (5%)		0/19 (0%)		0/20 (0%)
Ataxia	0/20 (0%)		0/19 (0%)		1/20 (5%)
Convulsion	0/20 (0%)		0/19 (0%)		1/20 (5%)
Dizziness	1/20 (5%)		1/19 (5.3%)		0/20 (0%)
Presyncope	1/20 (5%)		0/19 (0%)		0/20 (0%)
Headache	7/20 (35%)		10/19 (52.6%)		6/20 (30%)
Dysgeusia	4/20 (20%)		0/19 (0%)		1/20 (5%)
Peripheral sensory neuropathy	2/20 (10%)		0/19 (0%)		0/20 (0%)
Hemiparesis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Neuropathy peripheral	9/20 (45%)		1/19 (5.3%)		2/20 (10%)
Paraesthesia	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Syncope	0/20 (0%)		0/19 (0%)		1/20 (5%)
Psychiatric disorders
Agitation	0/20 (0%)		0/19 (0%)		1/20 (5%)
Libido decreased	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Panic attack	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Flat affect	0/20 (0%)		0/19 (0%)		1/20 (5%)
Insomnia	3/20 (15%)		6/19 (31.6%)		7/20 (35%)
Anxiety	1/20 (5%)		2/19 (10.5%)		2/20 (10%)
Sleep disorder	1/20 (5%)		0/19 (0%)		0/20 (0%)
Confusional state	1/20 (5%)		0/19 (0%)		2/20 (10%)
Depression	1/20 (5%)		3/19 (15.8%)		0/20 (0%)
Renal and urinary disorders
Dysuria	0/20 (0%)		0/19 (0%)		1/20 (5%)
Haematuria	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Urinary retention	1/20 (5%)		0/19 (0%)		0/20 (0%)
Chromaturia	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Bladder pain	0/20 (0%)		0/19 (0%)		1/20 (5%)
Renal pain	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Nephrolithiasis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Pollakiuria	1/20 (5%)		0/19 (0%)		0/20 (0%)
Reproductive system and breast disorders
Erectile dysfunction	0/20 (0%)		0/19 (0%)		1/20 (5%)
Menstruation irregular	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Benign prostatic hyperplasia	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Bartholin's cyst	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/20 (15%)		5/19 (26.3%)		2/20 (10%)
Dysphonia	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Hiccups	1/20 (5%)		2/19 (10.5%)		0/20 (0%)
Pleural effusion	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Rhinitis allergic	1/20 (5%)		0/19 (0%)		0/20 (0%)
Epistaxis	1/20 (5%)		0/19 (0%)		1/20 (5%)
Pulmonary haemorrhage	1/20 (5%)		0/19 (0%)		0/20 (0%)
Nasal congestion	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Dyspnoea	6/20 (30%)		4/19 (21.1%)		1/20 (5%)
Pulmonary embolism	1/20 (5%)		0/19 (0%)		0/20 (0%)
Dyspnoea exertional	0/20 (0%)		3/19 (15.8%)		1/20 (5%)
Wheezing	0/20 (0%)		2/19 (10.5%)		1/20 (5%)
Sinus congestion	1/20 (5%)		0/19 (0%)		1/20 (5%)
Skin and subcutaneous tissue disorders
Neurodermatitis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Generalised erythema	1/20 (5%)		0/19 (0%)		0/20 (0%)
Hyperhidrosis	1/20 (5%)		2/19 (10.5%)		1/20 (5%)
Skin lesion	0/20 (0%)		0/19 (0%)		1/20 (5%)
Alopecia	12/20 (60%)		1/19 (5.3%)		3/20 (15%)
Hyperkeratosis	1/20 (5%)		0/19 (0%)		0/20 (0%)
Seborrhoeic dermatitis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Eczema	1/20 (5%)		0/19 (0%)		0/20 (0%)
Scar	0/20 (0%)		0/19 (0%)		1/20 (5%)
Dermatitis	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Night sweats	0/20 (0%)		0/19 (0%)		1/20 (5%)
Pruritus generalised	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Skin exfoliation	0/20 (0%)		0/19 (0%)		1/20 (5%)
Vitiligo	2/20 (10%)		1/19 (5.3%)		0/20 (0%)
Ecchymosis	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Erythema	0/20 (0%)		2/19 (10.5%)		2/20 (10%)
Papule	0/20 (0%)		0/19 (0%)		1/20 (5%)
Rash generalised	0/20 (0%)		0/19 (0%)		2/20 (10%)
Skin disorder	1/20 (5%)		0/19 (0%)		0/20 (0%)
Skin hyperpigmentation	1/20 (5%)		0/19 (0%)		0/20 (0%)
Skin irritation	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Actinic keratosis	0/20 (0%)		0/19 (0%)		1/20 (5%)
Rash	16/20 (80%)		11/19 (57.9%)		17/20 (85%)
Urticaria	1/20 (5%)		2/19 (10.5%)		2/20 (10%)
Dry skin	2/20 (10%)		2/19 (10.5%)		0/20 (0%)
Mechanical urticaria	0/20 (0%)		1/19 (5.3%)		0/20 (0%)
Nail disorder	1/20 (5%)		1/19 (5.3%)		0/20 (0%)
Pruritus	13/20 (65%)		14/19 (73.7%)		15/20 (75%)
Rash erythematous	0/20 (0%)		2/19 (10.5%)		0/20 (0%)
Vascular disorders
Hypertension	0/20 (0%)		1/19 (5.3%)		1/20 (5%)
Deep vein thrombosis	1/20 (5%)		0/19 (0%)		1/20 (5%)
Lymphoedema	0/20 (0%)		0/19 (0%)		1/20 (5%)
Flushing	3/20 (15%)		5/19 (26.3%)		1/20 (5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.