Objective: To estimate the activity and tolerability of iniparib plus paclitaxel and carboplatin as initial therapy of uterine carcinosarcoma.
Methods: Eligible patients had advanced, persistent or recurrent carcinosarcoma of the uterus, measurable disease and no prior chemotherapy. Patients received paclitaxel 175 mg/m(2) IV over 3h followed by carboplatin area under the curve (AUC)=six over 30 min on day one of 21 day cycles plus iniparib 4 mg/kg IV over 1h twice weekly beginning on day one. Treatment continued until disease progression or adverse effects prohibited further therapy. Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used to grade adverse events. The primary endpoint was tumor response. The study was conducted with a 2-stage group sequential design, targeting 20 and 25 patients in each stage. The study was designed to distinguish between 45% versus 65% responding with alpha=10% and 90% power.
Results: Twenty-two patients were entered onto the study with five excluded from analysis, leaving 17 evaluable for analysis. Treatment resulted in the expected hematologic and non-hematologic toxicities of the paclitaxel-carboplatin backbone. The observed proportion responding was 23.5% (4/17 patients). The two-sided, 90% confidence interval for the true probability of response was 8.5-46.1%. The required minimal number of responses to proceed to second stage was eight.
Conclusions: Iniparib plus paclitaxel and carboplatin did not show significant activity to warrant further study. The rate of exclusion upon central pathology review (23%) suggests that review of pathology slides for confirmation of eligibility is important in this tumor type.
Trial registration: ClinicalTrials.gov NCT00687687.
Copyright © 2012 Elsevier Inc. All rights reserved.