The purpose of this study is to assess the effect of multiple-dose administration of rifampin on the single dose PK of pevonedistat in adult participants with advanced solid tumors.
The study will enroll approximately 20 participants. The study will be conducted in two Parts: Part A and optional Part B. Part A will have a drug-drug interaction (DDI) assessment. In Part A, participants will be assigned to: • Pevonedistat 50 mg/m\^2 + Rifampin Eligible participants from Part A will continue treatment in optional Part B with pevonedistat in combination with SoC chemotherapy, docetaxel or carboplatin plus paclitaxel. The investigator will decide which SoC combination partner a participant will receive. * Pevonedistat 25 mg/m\^2 + Docetaxel * Pevonedistat 20 mg/m\^2 + Carboplatin + Paclitaxel This multi-center trial will be conducted in the United States. The overall time to participate in this study is 18 months. Participants will make a final visit to the clinic 30 days after receiving their last dose of study drug or before the start of subsequent therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
20
Pevonedistat intravenous infusion.
Rifampin capsules.
Docetaxel intravenous infusion.
Emory University
Atlanta, Georgia, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Greenville Health System - Institute for Translational Oncology Research
Greenville, South Carolina, United States
Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
The Least square (LS) means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.
Time frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.
Time frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.
Time frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Part A: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
Time frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Part A: Volume of Distribution at Steady State After Intravenous Administration (Vss) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
Time frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Part A: Terminal Disposition Phase Half-life (T1/2z) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
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Carboplatin intravenous infusion.
Paclitaxel intravenous infusion.
Time frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment
Best overall response was defined as participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target and non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR: at least 30 percent (%) decrease in sum of diameter of target lesions, taking as reference baseline sum of diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum of diameter. PD: at least 20% increase in sum of diameter of target lesions, taking as reference, smallest sum on study.
Time frame: Up to Cycle 17 (end of treatment) (Cycle length =21 days)