Gemcitabine Hydrochloride and Oxaliplatin or Observation in Treating Patients With Biliary Tract Cancer That Has Been Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Observation is watching a patient's condition but not giving treatment until symptoms appear. It is not yet known whether giving gemcitabine hydrochloride together with oxaliplatin is more effective than observation in treating patients with biliary tract cancer that has been removed by surgery. PURPOSE: This randomized phase III trial is studying giving gemcitabine hydrochloride together with oxaliplatin to see how well it works compared with observation in treating patients with biliary tract cancer that has been removed by surgery.

Detailed Description
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OBJECTIVES: Primary Compare disease-free survival (DFS) of patients with resected biliary tract cancer treated with adjuvant gemcitabine hydrochloride and oxaliplatin versus clinical observation. Compare quality of life of these patients. Secondary Compare overall survival of these patients. Determine the toxicity of the chemotherapy in these patients. Explore prognostic factors for DFS including resection result (R0 vs R1), location of primary tumor (intrahepatic vs extrahepatic vs gallbladder), evolution of CA19-9, and lymph node involvement (N0 vs N+ and Nx). (Exploratory) Study pathological factors in surgical specimens to identify main characteristics and phenotypic clinicoanatomical biliary tract cancers before therapy. (Exploratory) Identify nontumor-associated liver injury and factors that may facilitate the emergence of biliary tract cancers. (Exploratory) Identify signaling pathways that may predict response to therapy. (Exploratory) Determine the molecular characteristics to differentiate tumors according to their position in the biliary tract (extrahepatic bile duct, intrahepatic cholangiocarcinoma site [hilar], and peripheral cholangiocarcinoma vesicle site). (Exploratory) OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive gemcitabine hydrochloride IV over 100 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 14 days for 12 courses. Arm II: Patients undergo clinical observation only every 4 weeks for 5 months. Quality of life is assessed at baseline, at 3 and 6 months, and then at all follow-up visits. After completion of study therapy, patients are followed up at 6 months, every 3 months for 2 years, and then every 6 months for 3 years.

Official Title
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Phase III Multicenter Randomized Study Comparing the Effect of Adjuvant Chemotherapy for Six Months With Gemcitabine-Oxaliplatin 85 mg/m2 (GEMOX 85) to Observation in Patients Who Underwent Surgery for Cancer of the Bile Ducts

Conditions
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Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Liver Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: oxaliplatin
* Other: clinical observation
* Procedure: adjuvant therapy
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the intrahepatic bile ducts, gallbladder, or extrahepatic bile ducts Mixed forms of hepatocholangiocarcinomas included provided the cholangiocarcinoma is predominant Underwent surgical resection of the disease (R0 or R1) at least 4 weeks but no more than 13 weeks ago Nonmetastatic disease as assessed by abdominal MRI and chest x-ray No cancer of the pancreas or duodenum invading the bile duct and ampulla of Vater PATIENT CHARACTERISTICS: ECOG performance status 0-2 Hemoglobin ≥ 10 g/dL (transfusion allowed) ANC ≥ 1,500/mm³ Platelet count ≥ 75,000/mm³ Creatinine clearance > 40 mL/min Prothrombin time > 60% OR INR < 1.5 (without anticoagulant therapy) Transaminases ≤ 5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Conjugated bilirubin ≤ 35 μmol/L (after biliary drainage, if necessary) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No contraindications to oxaliplatin and gemcitabine hydrochloride therapy Prior invasive cancer allowed provided it has been in complete remission for ≥ 5 years No other concurrent invasive cancer except adequately treated carcinoma in situ of the cervix or basal cell carcinoma No other severe, unresolved disease No mental illness No HIV positivity No grade 1 angina or symptomatic angina ≥ grade 2 No sensitive peripheral neuropathy No uncontrolled diabetes No inability to undergo medical tests due to geographical, social, or psychological reasons No prisoners or patients under guardianship No Child B or C cirrhosis PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior neoadjuvant chemotherapy or radiotherapy No prior organ transplantation No concurrent participation in another clinical trial of an experimental agent

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 |
| --- | --- |
| Experimental: ARM A: Gemox 85<br>Adjuvant chemotherapy for six months with gemcitabine - oxaliplatin 85mg / m² ( GEMOX 85) | Drug: gemcitabine hydrochloride<br> <br> Drug: oxaliplatin<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: quality-of-life assessment<br> <br> |
| Other: ARM B:<br>Observation until progression or death | Other: clinical observation<br> <br> Procedure: quality-of-life assessment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | up to 3 years | 
| Quality of life |  | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | up to 3 years | 
| Toxicity of adjuvant chemotherapy |  | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the extrahepatic bile duct, cholangiocarcinoma of the extrahepatic bile duct, liver and intrahepatic biliary tract cancer, localized extrahepatic bile duct cancer, adenocarcinoma of the gallbladder, cholangiocarcinoma of the gallbladder, localized gallbladder cancer