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

Primary Purpose

Advanced Melanoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ipilimumab
Carboplatin
Paclitaxel
Dacarbazine
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Melanoma focused on measuring Untreated Advanced Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Angeles Clinic & Research Inst.
  • H Lee Moffit Cancer Cnt And Res Inst
  • Memorial Sloan Kettering Cancer Center
  • Blumenthal Cancer Center, Carolinas Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Arm A

Arm B

Arm C

Arm Description

Outcomes

Primary Outcome Measures

Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population
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.
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
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

Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
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..
Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
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.
Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
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..
Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
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.
Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants
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.
Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants
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.
Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants
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.
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
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.
Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population
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).
Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population
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.
Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population
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.
Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population
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.
Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population
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
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population
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
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population
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
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population
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.
Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population
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.

Full Information

First Posted
November 20, 2008
Last Updated
December 31, 2013
Sponsor
Bristol-Myers Squibb
Collaborators
Medarex
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1. Study Identification

Unique Protocol Identification Number
NCT00796991
Brief Title
Drug-Drug Interaction - 3 Arm - Carboplatin/Paclitaxel, Dacarbazine
Official Title
A Randomized, Parallel, 3-arm Study to Characterize the Effect of Ipilimumab + Chemotherapy in Patients With Untreated Advanced Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
Collaborators
Medarex

4. Oversight

Data Monitoring Committee
No

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Melanoma
Keywords
Untreated Advanced Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Active Comparator
Arm Title
Arm B
Arm Type
Active Comparator
Arm Title
Arm C
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
BMS-734016, MDX-010
Intervention Description
Solution, intravenous, 10mg/kg, every 3 weeks in the induction phase, up to 4 doses in the induction phase, 48 weeks
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
BMY-26575, PARAPLATIN
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
TAXOL, BMS-181339
Intervention Description
Solution, intravenous, 175 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Intervention Description
Solution, intravenous, 850 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
The Angeles Clinic & Research Inst.
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
H Lee Moffit Cancer Cnt And Res Inst
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Blumenthal Cancer Center, Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States

12. IPD Sharing Statement

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

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