Phase I trial of oxaliplatin/irinotecan/S-1 (OX-IRIS) as first line chemotherapy for unresectable pancreatic cancer (HGCSG1403 study)

Background

A combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) is one of the standard first-line therapy in patients with unresectable pancreatic cancer. However, implanted central venous access port (CV-port) is essential for the treatment with FOLFIRINOX, so the therapy is somewhat less convenient and is often accompanied by CV-port related problems such as infection and thrombosis especially in case of pancreatic cancer. S-1 is an oral fluoropyrimidine derivative shown to be effective for pancreatic cancer in Japan. CV-port free treatment is feasible by replacing intravenous fluorouracil to orally S-1. Here we developed a new combination chemotherapy regimen consisting of oxaliplatin, irinotecan and S-1 (OX-IRIS).

Trial design

This is a dose-escalation phase I study in Japanese patients with unresectable pancreatic cancer using a standard 3 + 3 design followed by expansion cohorts. Key eligibility criteria are as follows: 1) Pathologically diagnosed invasive ductal carcinoma; 2) Unresectable locally advanced, metastatic, or recurrent disease; 3) No prior chemotherapy or radiotherapy for pancreatic cancer; 4) Aged 20 to 75 years old; 5) ECOG PS of 0 or 1. OX-IRIS regimen consists of 28-day cycles with escalated dose of oxaliplatin (50-85 mg/m² on day 1 and 15), irinotecan (100-180 mg/ m² on day 1 and 15) and S-1 (80 mg/m²/day on day 1 to 14). The primary end points are assessment of dose limiting toxicities (DLTs) and determination of maximum tolerated dose (MTD) to investigate the recommended dose (RD) in subsequent phase II study. Secondary endpoints are assessment of safety, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Response is evaluated by investigator by RECIST v1.1 every 6 weeks and adverse effect is monitored and graded according to CTCAE v4.0. MTD is evaluated in cycle 1. This study is recruiting in 2 sites in Japan and registered as UMIN0000170002.

Clinical trial identification

UMIN0000170002

Disclosure

All authors have declared no conflicts of interest.