Phase II Clinical Trial of Paclitaxel Loaded Polymeric Micelle in Patients with Advanced Pancreatic Cancer

ABSTRACT

Purpose: To determine in patients, with locally advanced or metastatic pancreatic cancer (APC), efficacy and safety of treatment with intravenous paclitaxel loaded polymeric micelle (GPM). Patients and methods: This was a multicenter, open-label Phase II study. Patients with APC, ECOG performance status ≤ 2, no prior chemotherapy and adequate organ function were treated with 3-hour GPM infusions every 3 weeks. Initial patients were treated with 435 mg/m² (n = 11). The dose was reduced for subsequent patients to 350 or 300 mg/m² (n = 45). Primary endpoint was time to tumor progression (TTP). Results: 56 patients were enrolled. Median TTP for patients treated with 300 or 350 mg/m² doses was 3.2 months (95% CI, 2.6–4.2). Median progression free survival (PFS) was 2.8 months (95% CI, 1.4–4.0). Median overall survival (OS) was 6.5 months (95% CI, 5.1–7.9). Among patients treated with above doses of GPM, there was 1 complete remission (CR) and 2 partial remissions (PR) with an overall response rate (ORR) of 6.7%. Disease control rate (CR + PR + stable disease) was 60.0%. Most common grade 3 toxicities were: neutropenia (40.0%), fatigue (17.8%), infection, dehydration, neuropathy (each 13.3%), and abdominal pain (11.1%). Conclusions: Treatment of APC with GPM at a dose of 300 mg/m² q 3 weeks was well tolerated and common toxicities were qualitatively similar to Cremophor-based paclitaxel. GPM monotherapy resulted in OS and other efficacy parameters preferable to that seen historically with gemcitabine. Future studies of GPM in combination with other agents for treatment of APC are warranted.