Trial Information

An Open-label, Single-centre, Single-arm Phase II Study of Capecitabine Combined With Oxaliplatin and Irinotecan (Xeloxiri) as First-line Treatment in Patients With Advanced Unresectable Pancreatic Adenocarcinoma

Pancreatic cancer carries extremely dismal overall prognosis that its motality was almost
the same as its incidence in 2008.[1] Pancreatic adenocarcinoma is the commonest type of
pancreatic cancer and was the fourth leading cause of cancer death in the United States in
2010.[2] For all stages combined, the 1- and 5-year relative survival rates are 26% and 6%,
respectively. Even for those people diagnosed with local disease, the 5-year survival is
only 23%.[3]

Gemcitabine (Gemzar®; Eli Lilly) has become the reference regimen for advanced pancreatic
cancer after a randomized trial showed significant improvement in overall survival as
compared with fluorouracil (5-FU) administered as an intravenous bolus.[4] Capecitabine
(Xeloda®; Roche) is an oral fluoropyrimidine carbamate prodrug designed to generate 5-FU
preferentially in tumor cells due to high concentration level of thymidine phosphorylase
enzyme. This allows to mimic continuous 5-FU infusion at the tumor site and to reduce
exposure of adjacent healthy tissues without causing discomfort and complications related to
intravenous (IV) administration.[5] It has been widely used for the treatment of colorectal
cancers and breast cancer.

Irinotecan (Campto®; Pfizer) has some clinical activity against advanced pancreatic cancer.
Preclinical studies have indicated that irinotecan has synergistic activity when it is
administered before 5-FU and leucovorin. Oxaliplatin (Eloxatin®; sanofi-aventis) has
clinical activity against pancreatic cancer only when combined with 5-FU. Oxaliplatin and
irinotecan show synergistic activity in vitro.[6]

A recent randomized controlled trial demonstrated that a combination of 5-FU, leucovorin,
irinotecan and oxaliplatin (Folfirinox regimen) was associated with a survival advantage and
had increased toxicity as compared to single-agent gemcitabine in pancreatic cancer
patients.[6] Another recent phase I trial showed promising results of the combination of
capecitabine, oxaliplatin and irinotecan in metastatic colorectal cancer subjects and
suggested that this tritherapy may provide valuable therapeutic alternative, especially in
patients with gastrointestinal cancer.[5]

Therefore, it is of interest to explore the possibility to replace IV 5-FU and leucovorin in
the Folfirinox regimen with capecitabine and to assess the efficacy and tolerability of this
modified regimen in treating patients with advanced unresectable pancreatic carcinoma.