Phase II study of intraperitoneal submicron particle paclitaxel (SPP) plus IV carboplatin and paclitaxel in patients with epithelial ovarian cancer undergoing cytoreductive surgery.

Abstract

e18046 Background: Although advances in chemotherapy, cytoreductive surgery, and maintenance therapy (SOC) improved PFS for high grade epithelial ovarian cancer, > 20% of patients relapse during the first 6 months and 60% relapse after 6 months. Submicron particles (~800 nm) of paclitaxel (SPP) contain 1-2 billion molecules of pure drug that release tumoricidal levels of paclitaxel over many weeks. In a previous trial, percutaneous instillations of SPP in nonsurgical patients with intraperitoneal cancer were associated with reduced systemic and local toxicity as compared to standard chemotherapy regimens. (Williamson et al Cancer Chemo Pharm (2015) 75:1075). Methods: This study compared two dose-levels of IP SPP instilled in 200 ml of saline post-cytoreductive surgery. Eligible patients with primary (n = 6) or recurrent (n = 4) epithelial ovarian cancer who underwent complete cytoreductive surgery were enrolled to receive a single instillation of IP SPP followed by standard IV carboplatin and paclitaxel. Endpoints were PFS and evaluation of treatment-emergent adverse events. Clinical response was determined by CT scans and serum CA-125 measurements. Results: Of the 24 subjects screened, 10 were enrolled and received treatment: seven patients received 100 mg/m2 and three received 200 mg/m2. For analysis purposes, 7 out of 10 subjects were evaluable (1 withdrew, 1 died unrelated to study drug during IV treatment and 1 was unevaluable). Upon completion of planned chemotherapy post-SPP instillation, the PFS at 6 months was 66% (4/6) and at 12-months 66% (4/6) using RECIST 1.1. One subject had a complete response at the end of IV treatment, but died (unrelated to study treatment) before PFS evaluation. There was one case of incision dehiscence and one case of vaginal cuff leakage after surgery. Conclusions: This pilot study supports further evaluation of IP SPP to treat peritoneal carcinomas. Clinical trial information: NCT03029585.