Phase I clinical trial of ixabepilone and pegylated liposomal doxorubicin in patients with advanced breast or ovarian cancers: New York Cancer Consortium Trial P7229

Abstract

2570 Background: Ixabepilone (IX) is a semisynthetic epothilone B analog with activity in patients (pts) with taxane refractory cancer. Two phase III clinical trials in breast cancer (BC) and a phase II study in ovarian cancer (OC) have recently been completed. Pegylated liposomal doxorubicin (PLD) is used for the treatment of platinum refractory OC and has activity in patients with metastatic BC. Methods: We have completed enrollment of a phase I study of PLD IV and ixabepilone IV over 3 hours. 18 pts with metastatic cancer (10 BC and 8 OC) with median age 51 were enrolled from 1/13/06 to 12/22/06. A total of 60 cycles has been administered to date. 3 OC patients enrolled at dose level 3 have not yet completed 2 cycles of treatment and are not yet evaluable. Results: Dose limiting toxicities (DLT) based on toxicities experienced during the first 2 cycles is provided in the table below. Adverse events (AE) occurring in any cycle were: Grade 4 AE: neutropenia < 7 days (1 pt). Grade 3 AE: palmar plantar erythrodysesthesia (PPE) (4), mucositis (3), infection (2), fatigue (2), neutropenia (2), thrombocytopenia (2), anemia (1), neuropathy (1), bilirubin (1). Non-hematological grade 2 AEs included: mucositis (4), PPE (3), infection (2), neuropathy (2), rash (3), pain (3), fever (1), myalgias (1), and anorexia (1). Responses so far for 10 BC pts are PR (1) SD (3) PD (6) and for 5 OC pts are PR (1) SD (2) PD (2). Updated results will be presented. Conclusions: Although the recommended phase II dose when given every 3 weeks is 30 mg/m2 for PLD and 32 mg/m2 for IX by our criteria, PPE and mucositis became problematic when treatment was continued beyond 2 cycles. We are therefore exploring a 4 week PLD schedule, evaluating IX given either every 4 weeks (as shown) or weekly (on days 1, 8, and 15). A phase II trial of the combination in platinum refractory OC will be initiated upon completion of the phase I. Supported by N01-CM-62204 [Table: see text] [Table: see text]