A phase II study of UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: A Princess Margaret Phase II Consortium Trial

3127 Background: The treatment of platinum-resistant recurrent ovarian cancer remains problematic with low response rates which are generally of short duration. The staurosporine derivate UCN-01 has been shown to potentiate the cytotoxicity of topotecan in preclinical models. To determine whether the clinical efficacy of topotecan, one of the standard agents used platinum-resistant ovarian cancer, could be enhanced, it was combined with the cell cycle inhibitor UCN-01. Methods: This phase II study was designed to evaluate the activity and toxicity profile of topotecan and UCN-01 in recurrent ovarian cancer. Patients were required to have measurable disease, 0–2 previous chemotherapy regimens for recurrent disease and performance status 0–2. Topotecan was administered at the phase II recommended doses of 1 mg/m2 iv on days 1 to 5, and UCN-01 at 70 mg/m2 iv on day 1 of the first cycle, and 35 mg/m2 iv on day 1 of subsequent cycles. Matched tumor biopsies have been obtained on 7 patients, pre-treatment and after the first cycle of therapy. Results: A total of 29 patients have been enrolled in the study, all of whom are evaluable for toxicity and response. Median age was 55 (23–72). All patients had received prior platinum and paclitaxel, median number of previous chemotherapy regimens being 2. The most commonly observed grade 3–4 toxicities were neutropenia (79%), anemia (41%), thrombocytopenia (14%), hyperglycemia (10%), febrile neutropenia (10%) and pain (10%). Patients received a median of 3 cycles (1–11). Three patients achieved a PR (10%), 15 SD (52%), and 9 PD (31%). Conclusions: The study criterion to proceed to stage 2 of the protocol required 4 PRs in the first 19 patients in stage 1. Since only 3 PRs have been achieved in the 29 patients, the combination of topotecan and UCN-01 has been deemed insufficiently active to proceed to stage 2 of the protocol and the study has been closed to further accrual. No significant financial relationships to disclose.