Study of PEP02 as a Second Line Therapy for Metastatic Pancreatic Cancer

The purpose of this study is to see the effect of PEP02 in the treatment of metastatic pancreatic cancer.

Gemcitabine monotherapy or a gemcitabine-based combination regimen is the standard first line therapy for advanced pancreatic cancer. After disease progression, there is no standard treatment available. In animal studies and a previous phase I trial, PEP02 has shown anti-tumor activity and preliminary efficacy in pancreatic cancer. In addition, a phase II study of free-form irinotecan single agent has already shown encouraging activity as second-line treatment for patients with advanced pancreatic cancer refractory to gemcitabine. The liposome formulation of PEP02 theoretically has therapeutic advantages over free-form irinotecan, such as site-specific delivery and extended release of drug. Hence PEP02 may be able to provide better efficacy than free-form irinotecan. The primary purpose of this phase II study is to evaluate the activity of PEP02 as a second-line therapy in patients with metastatic pancreatic cancer failed to gemcitabine treatment. The primary goal is to measure the 3-month survival rate. An optimal Simon's 2-stage design will be used for this exploratory phase II study.

120 mg/m2, IV infusion for 90 minutes on day 1 of each 21 days as a treatment cycle. Number of Cycles: until progression or unacceptable toxicity develops.

objective tumor response, PFS, duration of response, overall survival, tumor marker response of CA19-9, clinical benefit response

Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas Metastatic disease Documented disease progression after treatment with 1 line of prior gemcitabine-based regimen Karnofsky performance status equal or more than 70 Exclusion Criteria: With active CNS metastases With clinically significant gastrointestinal disorder (e.g., bleeding, inflammation, occlusion, or diarrhea > grade 1) Major surgery or radiotherapy within 4 weeks Prior participation in any investigational drug study within 4 weeks With prior irinotecan treatment

Ko AH, Tempero MA, Shan YS, Su WC, Lin YL, Dito E, Ong A, Wang YW, Yeh CG, Chen LT. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. Br J Cancer. 2013 Aug 20;109(4):920-5. doi: 10.1038/bjc.2013.408. Epub 2013 Jul 23.