Phase 1
N=59
Drug-Drug Interaction - 3 Arm - Carboplatin/Paclitaxel, Dacarbazine
Advanced Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT00796991 ↗Enrolled (actual)
59
Serious AEs
61.0%
Results posted
Jan 2014
Primary outcome: Primary: Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population — 234.54; 246.50; 251.05; 3.35 µg/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Ipilimumab (Drug); Carboplatin (Drug); Paclitaxel (Drug); Dacarbazine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Nov 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population |
234.54; 246.50; 251.05; 3.35; NA; NA | — |
| PRIMARY 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 |
46925.36; 49569.06; 54039.79; 12.37; NA; NA | — |
| SECONDARY Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population |
1.51; 4.00; 1.56; 3.00; NA; NA | — |
| SECONDARY Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population |
13.93; 13.39; 15.25; 10.26; NA; NA | — |
| SECONDARY Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population |
11.63; 11.17; 10.23; 27.87; NA; NA | — |
| SECONDARY Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population |
5.10; 4.88; 5.05; 205.63; NA; NA | — |
| SECONDARY Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants |
1; 1; 0; 1; 4; 5 | — |
| SECONDARY Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants |
1; 1; 0; 4; 5; 5 | — |
| SECONDARY Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants |
2; 5; 5; 8; 10; 9 | — |
| SECONDARY 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 |
20; 19; 20; 9; 8; 9 | — |
| SECONDARY Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population |
1.19; 1.41; 1.28; 1.62; 2.05; 1.56 | 0.027 sig |
| SECONDARY Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population |
10.0; 6.6; 4.9; 2.0; 7.0; 8.5 | — |
| SECONDARY Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population |
24.0; 0.3; -0.7; -3.0; -9.5; 7.5 | — |
| SECONDARY Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population |
0; 1.4; -0.8; -2.0; -2.7; -1.3 | — |
| SECONDARY Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population |
-0.5; -0.1; 0.2; 0.4; 0.0; -0.2 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population |
3; 4; 5; 9; 13; 10 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population |
8; 13; 17; 4; 4; 1 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population |
4; 5; 6; 12; 13; 11 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population |
20; 18; 19; 0; 0; 1 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population |
20; 18; 19; 0; 0; 1 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population |
20; 19; 18; 0; 0; 2 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population |
18; 18; 16; 2; 1; 3 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population |
18; 18; 15; 2; 1; 4 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population |
17; 14; 14; 3; 5; 6 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population |
14; 18; 18; 6; 1; 0 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population |
20; 17; 18; 0; 1; 2 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population |
20; 17; 17; 0; 2; 1 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population |
20; 19; 16; 0; 0; 2 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population |
18; 19; 19; 2; 0; 1 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population |
12; 6; 4; 1; 0; 0 | — |
| SECONDARY Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population |
20; 19; 17; 0; 1; 3 | — |
Summary
The purpose of this clinical research study is to learn the pharmacokinetics of Ipilimumab when combined with Paclitaxel/Carboplatin or Dacarbazine
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
Data sourced from ClinicalTrials.gov (NCT00796991). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.