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

Study Overview
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Brief Summary
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The primary objective is to investigate the objective response rate in patients receiving GEMOX (gemcitabine plus oxaliplatin) plus cetuximab as first line treatment in advanced or metastatic unresectable BTC biliary tract cancer compared to patients receiving the same chemotherapy without cetuximab. The secondary objectives include the exploration of the effect of the multimodality strategy on progression-free and overall survival, biomarker prediction, and toxicity.

Detailed Description
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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).

Official Title
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A Randomized Phase II Study of Gemcitabine Plus Oxaliplatin (GEMOX) With or Without Cetuximab in Locally Advanced and Metastatic Biliary Tract Cancer (BTC)

Conditions
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Cholangiocarcinoma, Adenocarcinoma of Gallbladder

Intervention / Treatment
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* Drug: gemcitabine, oxaliplatin
* Drug: cetuximab, gemcitabine, oxaliplatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GEMOX<br>Intravenous infusion of gemcitabine 800 mg/m2 at a fixed rate of 10 mg/m2/min followed by oxaliplatin 85 mg/m2 2-hour infusion, every 2 weeks. | Drug: gemcitabine, oxaliplatin<br>* GEMOX (intravenous infusion of gemcitabine 800 mg/m2 at a fixed rate of 10 mg/m2/min followed by oxaliplatin 85 mg/m2 2-hour infusion, every 2 weeks<br>* Other names: Gemmis, Eloxatin;|
| Experimental: E-GEMOX<br>Arm A will receive E-GEMOX with additional intravenous infusion of cetuximab (120 minutes for the 1st, 90 minutes for the 2nd and 60 minutes for all subsequent infusions) before GEMOX will be administered as above. | Drug: cetuximab, gemcitabine, oxaliplatin<br>* E-GEMOX: intravenous infusion of cetuximab (120 minutes for the 1st, 90 minutes for the 2nd and 60 minutes for all subsequent infusions) before GEMOX will be administered as above. All of the study medication will be administrated on day 1 every 2 weeks, which is regarded as one cycle.<br>* Other names: Erbitux@, Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | Evaluation of tumor response according to RECIST 1.1 version Evaluation will be done at baseline and every 8 weeks. Evaluation will be performed with CT or MRI. | baseline and every 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The toxicity profiles of the combination treatments | Treatment toxicity will be graded by NCI Common Toxicity Criteria Version 4.0 (CTC, v4.0) for safety evaluation | Baseline and every 2 weeks, | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biliary tract cancer, BTC, cetuximaba