A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

Background: Patients with recurrent ovarian cancer have limited options, especially in the context of relapse less than six months from primary platinum-based therapy. This Gynecologic Oncology Group (GOG) study was conducted to evaluate the impact of the histone deacetylase inhibitor, belinostat, in combination with carboplatin in women with platinum-resistant ovarian cancer.

Methods: Eligible patients had measurable, recurrent disease within six months of their last dose of a platinum-based combination. Belinostat was dosed at 1000 mg/m(2) daily for five days with carboplatin AUC 5 on day three of 21-day cycles. The primary endpoint was overall response rate (ORR), using a two-stage design.

Results: Twenty-nine women enrolled on study and 27 were evaluable. The median number of cycles given was two (range 1-10). One patient had a complete response and one had a partial response, for an ORR of 7.4% (95% CI, .9%-24.3%). Twelve patients had stable disease while eight had increasing disease. Response could not be assessed in five (18.5%). Grade 3 and 4 events occurring in more than 10% of treated patients were uncommon and limited to neutropenia (22.2%), thrombocytopenia (14.8%), and vomiting (11.1%). The median progression-free survival (PFS) was 3.3 months and overall survival was 13.7 months. PFS of at least six months was noted in 29.6% of patients. Due to the lack of drug activity, the study was closed after the first-stage.

Conclusions: The addition of belinostat to carboplatin had little activity in a population with platinum-resistant ovarian cancer.