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

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.

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