An open-label, single-arm Phase II study of intravenous weekly (Days 1 and 8) topotecan in combination with carboplatin (Day 1) every 21 days as second-line therapy in patients with platinum-sensitive relapsed ovarian cancer.

ABSTRACT

OBJECTIVE: To evaluate clinical activity of weekly topotecan plus carboplatin in patients with platinum-sensitive recurrent ovarian, fallopian tube, or peritoneal carcinoma. METHODS: An open-label, single-arm, multicenter Phase I/II study. Phase II was the activity assessment phase, with overall response rate (ORR) as the primary endpoint. Eligible patients (females aged ≥18 years) received study treatment at the maximum-tolerated dose (MTD) identified in Phase I intravenous topotecan 2.5mg/m(2) (Days 1 and 8), followed by carboplatin AUC 5 (Day 1), every 21 days. A two-stage Green-Dahlberg design was used to assess efficacy of treatment. An ORR of ≤30% was required to conclude that treatment was ineffective. RESULTS: Twenty-two patients in Phase I permitted identification of the MTD. In Phase II, 55 patients (median age 64.0 years) were enrolled and included in the intent-to-treat population. There were six complete responses (10.9%) and 11 partial responses (20.0%), giving an ORR of 30.9% (17 patients; 95% CI 18.7%, 43.1%). Median time to response and progression-free survival were 6.57 weeks (95% CI 5.86, 12.57) and 44.29 weeks (95% CI 36.14, 52.14), respectively. Grade 3/4 hematological toxicity caused dose reductions, treatment delays and study discontinuation. Neutropenia (Grade 3 29%; Grade 4 11%) was the most common hematological adverse event (AE). Fatigue (71%) and nausea (71%) were the most common drug-related non-hematologic AEs. CONCLUSIONS: This study showed an acceptable benefit-risk profile for topotecan plus carboplatin. Further studies using alternative dose levels could help define an optimal dosing schedule for this treatment combination in patients with platinum-sensitive recurrent disease.