A Randomized Study of GEMOX With or Without Cetuximab in Locally Advanced and Metastatic BTC

It is considered realistic, that within 18 months 120 patients can be included in the participating centers. Based on the previous publications an objective response rate (ORR) of 20% is expected in the GEMOX arm (Arm B). When the sample size of evaluable patients is between 110 and 120 evaluable patients (ie. 55 to 60 patients per treatment arm), then a two-sided 95% confidence interval (CI) for the difference between an arm B response rate PB, of 20% and an arm A response rate PA of 30%, 35% or 40% based on the large sample normal approximation will have a width between 15.4% and 16.7%. We assume an objective response rate of 30% for Arm A, then a two-sided 95% confidence interval (CI) for the difference between an arm B response rate PB, of 20% and an arm A response rate PA of 30% will have a width ±15.4% when the sample size of evaluable patients is 120 (i.e., 60 patients per treatment arm).

Inclusion criteria

• Cyto-/histological confirmed unresectable, locally advanced, or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma or adenocarcinoma of gallbladder, but NOT other peri-ampulla Vateri or mixed tumor.
• At least one, not previously irradiated, measurable lesion according to RECIST (version 1.1).
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
• Aged no less than 20 years, at the time of acquisition of informed consent.
• Life expectancy >= 3 months.
• Adequate organ and bone marrow function as defined below: WBC >= 3.00 × 103/L and absolute neutrophil count >= 1.50 × 103/L, Platelet count >= 100 × 103/L, Hemoglobin level >= 10 g/dL, Serum creatinine <= 1.5 x Upper Normal Limit (UNL) and calculated GFR >= 40mL/min, Serum bilirubin <= 1.5 x UNL , ALT <= 2.5x UNL.
• Ability to understand and willingness to sign written Informed Consent Form.

Exclusion criteria

• Other anti-tumor agent such as systemic chemotherapy, immunotherapy or EGFR/VEGF-pathway-targeting therapy before the commencement of study treatment.
• Radiotherapy (except palliative irradiation of bone lesions) within 4 weeks before the commencement of study treatment.
• Other cancer or prior treatment for other carcinomas within the last five years, except cured non-melanoma skin cancer and treated in-situ cervical cancer.
• Known CNS metastasis.
• Major surgery within 4 weeks prior to start of study treatment (diagnostic biopsy, laparotomy, line placement is not considered as major surgery).
• Pre-existing peripheral neuropathy >= grade 2.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in the past 12 months, active gastrointestinal bleeding, central nervous system disorders or psychiatric illness/social situation that would limit compliance with study requirements or judged to be ineligible for the study by the investigator.
• Having received any investigational agents or participated in any investigational drug study within 4 weeks prior to study enrollment.
• Pregnant or breast-feeding female (a pregnancy test must be performed on all female patients who are of child-bearing potential before entering the study, and the result must be negative).
• Poor compliance.