Combined biological treatment and chemotherapy for patients with inoperable cholangiocarcinoma.

TPS217 Background: Cholangiocarcinoma (CC) is a relatively rare cancer with a severe prognosis. There are no standard chemotherapy to offer incurable patients, but regimes combining cisplatin and gemcitabine are commonly used based on preliminary phase III data. In Denmark, a combination of gemcitabine, oxaliplatin and capecitabine has been evaluated in phase I and phase II trials. Based on experience with other gastrointestinal tumors, there seems to be an additional effect when combining chemotherapy and epithelial growth factor receptor (EGFR) antibodies. Effect of EGFR inhibitors is only seen if the down-stream signalling protein KRAS is not mutated. 50% of CC are expected to hold KRAS mutations. The purpose of the trial is to evaluate the specific anti-tumor effect of (i) chemotherapy and panitumumab in CC without KRAS mutations and (ii) chemotherapy alone in patients with KRAS mutations. Methods: Eligibility criteria are made to reflect daily clinical practice and diminish selection bias by allowing inclusion of patients with performance status 2, age up to 80 years, and evaluable (not necessarily measurable) disease. Furthermore, histopathology only needs to be consistent with adenocarcinoma arisen from bile ducts together with a radiologic diagnosis of CC. The study is designed as two parallel phase II trials selected by KRAS status. In each trial a two-stage design is chosen with inclusion of 15-18 patients in stage one and 25-33 patients in stage II. All patients receive gemcitabine 1000 mg/m2 and oxaliplatin 60 mg/m2 on day one plus capecitabine 1000 mg/m2 b.i.d. day one to seven on a two weeks cycle. If KRAS wild-type panitumumab 6 mg/kg is given day one. The primary endpoint is progression free survival and secondary endpoints response rate, toxicity, and overall survival. During the trial tumor tissue and regular blood tests are collected for future translational research. Accrual began in September 2008 and is considerably higher in the panitumumab group, where the last patient is expected to be included in mid-2010. Surprisingly, only 5-10% have KRAS mutation and this part of the study will continue longer. Results will be reported separately. No significant financial relationships to disclose.