Fluorouracil, Cisplatin, and Radiation Therapy or Gemcitabine and Oxaliplatin in Treating Patients With Nonmetastatic Biliary Tract Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, oxaliplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving fluorouracil and cisplatin together with radiation therapy is more effective than giving gemcitabine together with oxaliplatin in treating nonmetastatic biliary tract cancer. PURPOSE: This randomized phase II/III trial is studying fluorouracil, cisplatin, and radiation therapy to see how well they work compared to gemcitabine and oxaliplatin in treating patients with nonmetastatic biliary tract cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Compare the 3-month progression rate in patients with unresectable, nonmetastatic cancer of the biliary tract treated with fluorouracil, cisplatin, and radiotherapy vs gemcitabine hydrochloride and oxaliplatin. (phase II) Compare the overall survival of patients treated with these regimens. (phase III) Secondary Compare toxicities of these regimens in these patients. (phase II) Compare the quality of life at initial drainage (phase II) and overall (phase III) of patients treated with these regimens. Compare the biliary complication rate in patients treated with these regimens. Compare the duration of hospitalization of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease location (gallbladder vs intrahepatic biliary duct vs extrahepatic biliary duct). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo radiotherapy once daily, 5 days a week on days 1-33. Patients also receive fluorouracil IV continuously over 5 days once a week in weeks 1-5 and cisplatin IV over 15 minutes on days 1-4 and 29-32 (or days 1 or 2 and 29 or 30) in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive gemcitabine hydrochloride IV over 100 minutes and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and then every 3 months thereafter. After completion of study therapy, patients are followed periodically for 2 years. PROJECTED ACCRUAL: A total of 170 patients will be accrued for this study.

Official Title
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Randomized Phase II-III Study of Chemoradiation With Fluorouracil and Cisplatin Versus Chemotherapy (Gemcitabine/Oxaliplatin) in Non Resectable But Non Metastatic Cancer of the Biliary Tract

Conditions
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Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Liver Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: gemcitabine hydrochloride
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of cancer of the biliary tract by 1 of the following methods: Histologic confirmation Stenosis of the biliary tract by MRI, CT scan, or ECHO Unresectable disease Amenable to radiotherapy No visceral metastases by imaging Hepatic adenopathies that can be included in a radiation field allowed No known ampulla of Vater or pancreatic cancer involving the biliary tract PATIENT CHARACTERISTICS: WHO performance status 0-2 Creatinine < 1.5 mg/dL Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 75,000/mm^3 Prothrombin time > 70% Bilirubin ≤ 2.9 mg/dL (after hepatic draining, if needed) No unstable angina No symptomatic cardiac insufficiency No other comorbidity that would preclude study therapy No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix No prior hydatid cyst or alveolar echinococciasis Not pregnant or nursing PRIOR CONCURRENT THERAPY: No recent biliary surgery No hepatic intra-arterial chemotherapy No prior anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Radio-chimiothérapie<br>Radio-chimiothérapie | Drug: cisplatin<br> <br> |
| Experimental: GEMOX<br>GEMOX | Drug: gemcitabine hydrochloride<br> <br> Drug: oxaliplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression rate at 3 months |  | 2012 | 
| Overall survival |  | 2012 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 2012 | 
| Biliary complication rate |  | 2012 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized unresectable adult primary liver cancer, unresectable extrahepatic bile duct cancer, unresectable gallbladder cancer