Phase I open-label trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases (IPGP study): study protocol

INTRODUCTION: Gastric cancer with peritoneal metastasis has a poor outcome. Only a few studies have specifically investigated this group of patients. Japanese researchers have shown that chemotherapy with intraperitoneal paclitaxel (IPP) and oral S-1 (tegafur/gimeracil/oteracil) is active and well tolerated. These results have been achieved in a specific genetic pool (Japanese population), using regimens that may not be available in other parts of the world. We have designed this phase I trial to investigate IPP in combination with a standard chemotherapy combination in these patients. METHODS: We use a 3+3 expanded cohort dose escalation until a predefined number of dose-limiting toxicities are reached. Patients will have an intraperitoneal catheter placed surgically after trial enrolment. Chemotherapy includes a maximum of six cycles (21 days) of capecitabine (X) (1000 mg/m(2) two times a day, days 1–14)+cisplatin (C) (intravenous 80 mg/m(2) day 1) and IPP (days 1 and 8) with the following doses: cohort-1: 10 mg/m(2), cohort-2: 20 mg/m(2) and cohort-3: 30 mg/m(2). Primary endpoint is to determine the maximum tolerated dose of IPP. Secondary endpoints include determining the safety and tolerability of IPP in combination with C and X, overall response rates, ascites response rate, progression-free survival, overall survival and effects on quality of life. Important inclusion criteria include age ≥18 years, human epidermal growth factor receptor 2 non-amplified gastric adenocarcinoma with histological or cytology-proven peritoneal involvement and adequate organ function. Exclusion criteria include previous malignancy within 5 years, recent abdominal or pelvic radiation treatment, significant abdominal adhesions or sepsis. ETHICS AND DISSEMINATION: The study is approved by Southern Adelaide Clinical Human Research Ethics Committee. A manuscript will be prepared for publication on the completion of the trial. This study will be conducted according to the Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) annotated with TGA comments (Therapeutic Goods Administration DSEB July 2000) and in compliance with applicable laws and regulations. The study will be performed in accordance with the NHMRC Statement on Ethical Conduct in Research Involving Humans (© Commonwealth of Australia 2007), and the NHMRC Australian Code for the Responsible Conduct of Research (©Australian Government 2007), and the principles laid down by the World Medical Assembly in the Declaration of Helsinki 2008. TRIAL REGISTRATION NUMBER: ACTRN12614001063606.