Evaluating the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors
The purpose of this study is to investigate whether ketoconazole, taken orally, influences the level of eribulin in the blood when the two drugs are given at the same time. The study will enroll patients with solid tumors whose cancer became worse even after standard treatment, or for whom there is no standard treatment available. The study will also investigate whether eribulin given together with ketoconazole is safe (has few side-effects) and is effective against cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label, Phase I Study to Evaluate the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors|
- PK sampling days 1 to 7 and 15 to 21 in Cycle 1 only. An extra predose blood sample to predict cytochrome P450 (CYP) 3A4 and (CYP) 3A5 phenotype [ Time Frame: 28 days ] [ Designated as safety issue: No ]
- Safety and tolerability of eribulin co-administered with oral ketoconazole. Safety and tolerability of eribulin given alone on Days 1 and 8 of a 21-day schedule. [ Time Frame: monitored throughout ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2009|
|Study Completion Date:||September 2009|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
Drug: eribulin and ketoconazole
Group 1: Treatment Cycle 1: intravenous (IV) eribulin alone is given on Day 1 at dose level of 1.4. mg/m^2 and on Day 15 at a reduced dose level of 0.7 mg/m^2 when oral ketoconazole 200 mg is also given. Ketoconazole is given 1 hour before eribulin administration and alone on Day 16 (23 hours later). The first cycle lasts 28 days.
Group 2: Treatment Cycle 1: IV eribulin is given at a dose of 1.4 mg/m^2 on Day 1. Oral ketoconazole is given on the same day at a dose of 200 mg 1 hour before eribulin administration. Ketoconazole alone is given on Day 2 (23 hours later), and eribulin alone is given on Day 15.
Treatment Cycle 2 onwards: intravenous eribulin alone is given on Days 1 and 8, every 21 days at dose level of 1.4 mg/m^2.