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

NCT00796991 | Completed Phase 1 Results

• 1 other identifier: CA184-078
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Advanced Melanoma

Keywords

Untreated Advanced Melanoma

Outcome Measures

Primary Outcomes (2)

• 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.

  Day 1 (0 h) to Day 43

• 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.

  Day 1 (0 h) to Day 43

Secondary Outcomes (29)

• 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

• 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

• Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

  Day 1 (0 h) to Day 43

• 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

• Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants

  Day 1 to Week 48

Study Arms (3)

Arm A

ACTIVE COMPARATOR

Drug: Ipilimumab; Drug: Carboplatin; Drug: Paclitaxel

Arm B

ACTIVE COMPARATOR

Drug: Ipilimumab; Drug: Dacarbazine

Arm C

ACTIVE COMPARATOR

Drug: Ipilimumab

Interventions

Ipilimumab DRUG

Solution, intravenous, 10mg/kg, every 3 weeks in the induction phase, up to 4 doses in the induction phase, 48 weeks

Also known as: BMS-734016, MDX-010

Arm A; Arm B; Arm C

Carboplatin DRUG

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

Also known as: BMY-26575, PARAPLATIN

Arm A

Paclitaxel DRUG

Solution, intravenous, 175 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks

Also known as: TAXOL, BMS-181339

Arm A

Dacarbazine DRUG

Solution, intravenous, 850 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Medarex: collaborator

Study Sites (4)

The Angeles Clinic & Research Inst.

Los Angeles, California, 90025, United States

Location

H Lee Moffit Cancer Cnt And Res Inst

Tampa, Florida, 33612, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Blumenthal Cancer Center, Carolinas Medical Center

Charlotte, North Carolina, 28204, United States

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Interventions

Ipilimumab; Carboplatin; Paclitaxel; BMS 181339; Dacarbazine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2008
• First Posted: November 24, 2008
• Study Start: February 1, 2009
• Primary Completion: November 1, 2009
• Study Completion: October 1, 2012
• Last Updated: January 6, 2014
• Results First Posted: January 6, 2014

Record last verified: 2013-12

Locations

US (4)