A multinational phase II study of liposome irinotecan (PEP02) for patients with gemcitabine-refractory metastatic pancreatic cancer

[[abstract]]Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11) that has improved pharmacokinetics and tumor biodistribution of both CPT-11 and its active metabolite-SN38 compared to the free form drug. PEP02 has showed encouraging safety and efficacy in various tumor types, including significant antitumor activity in a human pancreatic cancer L3.6pl orthotopic nude mouse xenograft model. In previous phase I studies, PEP02 either alone or in combination with 5-FU/LV demonstrated prolonged disease control in 5 of 7 (71%) patients (pts) with gemcitabine (GEM)-refractory advanced pancreatic cancer (PC). This phase II study aims to evaluate PEP02 monotherapy as 2nd-line treatment in pts with metastatic, GEM-refractory PC. Methods: Pts were eligible if they had metastatic pancreatic adenocarcinoma, KPS ? 70, and progressed following one line of GEM-based therapy. Treatment consisted of PEP02 120 mg/m2 administered as a 90-minute infusion every 3 weeks. A Simon's 2-stage design was used with 16 pts in the first stage and 39 pts in total; primary objective was 3-month survival rate (OS3-month). Results: Between March 2009 and August 2010, 37 pts were enrolled at 3 centers in the U.S. and Taiwan. Characteristics for the first 31 evaluable pts: 13 M/18 F; age 39-82 yrs; 19 Asian/12 Caucasian, KPS 100/90/80/70: 5/14/4/8. Mean number of treatment cycles is 5 (range, 1-22). Disease control rate (minor response + stable disease >2 cycles) is 52%. 8 of 24 pts (33%) with elevated baseline CA19-9 have had >50% biomarker decline. To date, 23/31 pts (74%) have survived > 3 months, with 4 pts still alive after 1 year. Reasons for study discontinuation: 74% progressive disease, 9% drug-related toxicity, 17% other. Preliminary safety data is available for the first stage. Most common G3/4 adverse events included: fatigue (31%), neutropenia (25%), nausea/vomiting (19%), and diarrhea (13%). Conclusions: This study has already met its primary endpoint (predicted OS3-month >65%). PEP02 appears to have both activity and tolerable side effects for pts with metastatic, GEM-refractory PC, and represents a promising option for this pt population with few standard options