Clinical trial NCT01133756
Conditions: Ovarian Cancer
Sponsor: Eisai Inc.
Start date: 2010-03-01; Completion date: 2012-09-01
Enrollment: 7 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study was to determine the maximum tolerated dose (MTD)/recommended Phase II dose of lenvatinib administered in combination with carboplatin and gemcitabine (Phase IB) and to evaluate the safety and tolerability of E7080 administered in combination with carboplatin and gemcitabine compared to carboplatin and gemcitabine alone (Phase II) in participants with platinum-sensitive recurrent ovarian cancer.

Detailed description:
This open-label, multicenter, randomized study was to consist of a Phase 1b portion: a safety run-in period with 3 doses of lenvatinib administered in combination with carboplatin + gemcitabine; and a Phase II portion: a randomized 2-arm period. Approximately 100 participants with ovarian cancer were to be enrolled in the study (10 to 20 participants in the Phase 1b portion and 80 participants in the Phase II portion). Participants were to participate in either the Phase 1b or the Phase II portion. Participants were to receive study treatment (lenvatinib plus carboplatin + gemcitabine or carboplatin + gemcitabine) for six 21-day cycles (18 weeks). Participants who receive E7080 and experience evidence of clinical benefit (CR, PR, or SD) may continue single agent E7080 beyond 18 weeks, until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, or withdrawal by investigator, whichever occurs first.

Initially, an ascending dose schedule starting at lenvatinib 16 mg once daily on Day 1 to Day 21 was chosen for the Phase 1b portion to determine the MTD of lenvatinib administered once daily in combination with carboplatin + gemcitabine; however, due to hematologic toxicity observed in the first cohort, the lenvatinib administration schedule was changed to Days 2 to 21 in Protocol Amendment 2. Continued hematologic toxicity prompted a third protocol amendment, designed to evaluate a lower range of doses starting at lenvatinib 8 mg once daily in Protocol Amendment 3.

After three protocol amendments, recruitment into the Phase 1b portion of the study was very limited, with only one evaluable participant enrolled during the last 5 months of recruitment. Due to the limited enrollment despite significant diligence to boost enrollment and the complex study design required to manage hematologic toxicity, the study was terminated before the initiation of Phase II.

Safety was assessed by the monitoring and recording of all adverse events (AEs) and serious adverse events (SAEs); vital signs; Gynecological Oncology Group performance status; clinical laboratory evaluations; physical examinations; and 12-lead electrocardiograms (ECGs).

Arms: arm 1: Phase IB and Phase II arm 2: Phase II
Interventions: intervention 1: Lenvatinib intervention 2: Carboplatin intervention 3: Gemcitabine
Intervention descriptions: intervention 1: lenvatinib (as 1mg, 4mg, and 10mg tablets) was administered orally, once daily continuously for each 21-day treatment cycle. intervention 2: Carboplatin was to be administered on Day 1 of every 21-day cycle at a dose AUC 4 over 30 minutes. intervention 3: Gemcitabine was to be administered on Day 1 and Day 8 of every 21-day cycle at a dose of 1000 mg/m2 over 30 minutes.

Protocol documents: