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

This study has been completed.
Sponsor:
Collaborator:
Medarex
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00796991
First received: November 20, 2008
Last updated: December 31, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Advanced Melanoma
Drug: Ipilimumab
Drug: Carboplatin
Drug: Paclitaxel
Drug: Dacarbazine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

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 [ Time Frame: Day 1 (0 h) to Day 43 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (0 h) to Day 43 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (0 h) to Day 43 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (0 h) to Day 43 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (0 h) to Day 43 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 (0 h) to Day 43 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day to Week 12 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to Week 48 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 72
Study Start Date: February 2009
Study Completion Date: October 2012
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00796991

Locations
United States, California
The Angeles Clinic & Research Inst.
Los Angeles, California, United States, 90025
United States, Florida
H Lee Moffit Cancer Cnt And Res Inst
Tampa, Florida, United States, 33612
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
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
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00796991     History of Changes
Other Study ID Numbers: CA184-078
Study First Received: November 20, 2008
Results First Received: November 5, 2013
Last Updated: December 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
Untreated Advanced Melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014