A phase I study of lenalidomide in combination with liposomal doxorubicin in recurrent epithelial ovarian cancer.

Abstract

e15545 Background: Lenalidomide (CC-5013) is an anti-angiogenic and immunomodulatory (IMiD) drug. The objective of this phase I clinical trial was to determine the maximum-tolerated dose (MTD), safety, and tolerability of lenalidomide in combination with liposomal doxorubicin in patients with recurrent epithelial ovarian cancer. Methods: Eligible patients had recurrent or progressive epithelial ovarian, fallopian tube, or primary peritoneal cancer. Dose escalation through five dose levels (10 mg, 15 mg, 20 mg, 25 mg, 30 mg) was planned with lenalidomide on days 1-28 of a 28 day cycle in combination with liposomal doxorubicin at a fixed dose (40 mg/m2) on day 1. Dose escalation was scheduled in cohorts of 3 patients enrolled at each dose level. Dose-limiting toxicity (DLT) was defined as grade 4 hematologic toxicities, or grade 3 or 4 non-hematologic toxicities which prevented the completion of cycle 1 or inability to start cycle 2 within 7 days of the scheduled start. Results: Eleven of 13 enrolled patients were eligible to participate in the trial. Five were enrolled at dose level 1 and 6 were enrolled at dose level 2. No DLTs occurred at level 1. Two DLTs occurred at level 2 due to urticaria and neurologic side effects (blurred vision, ataxia, and dizziness). At dose level 1, one patient had grade 3 neutropenia. At dose level 2, one patient had grade 4 neutropenia, one patient had grade 3 anemia, two patients had grade 3 or 4 fatigue, and one patient had grade 3 neurologic side effects. MTD was reached at dose level 1 of lenalidomide (10 mg) in combination with liposomal doxorubicin (40 mg/m2). There were no clinically significant drug-drug interactions. Conclusions: The combination of lenalidomide at 10 mg on days 1-28 and liposomal doxorubicin at 40 mg/m2 on day 1 resulted in an acceptable safety profile for the outpatient treatment of women with recurrent or progressive epithelial ovarian cancer. Further evaluation of lenalidomide at the MTD in combination with liposomal doxorubicin is warranted in a phase II trial.