Capecitabine or Observation After Surgery in Treating Patients With Biliary Tract Cancer

OBJECTIVES:

Primary

• To determine whether adjuvant chemotherapy with capecitabine has any effect on 2-year survival compared to expectant treatment alone (observation) in patients who have undergone a macroscopically complete surgical resection of a biliary tract cancer.

Secondary

• To compare capecitabine versus observation in terms of 5-year survival, relapse-free survival, toxicity, quality of life, and health economics.

OUTLINE: This is a multicenter, prospective, randomized study. Patients are stratified according to surgical center, disease site (hilar/extrahepatic cholangiocarcinoma vs intrahepatic cholangiocarcinoma vs gallbladder vs intrapancreatic/common bile duct), type of resection (R0 vs R1), and ECOG performance status (0 vs 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral capecitabine twice a day on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo expectant treatment (observation). Quality of life is assessed at baseline, every 3 months for 1 year, and then every 6 months for 1 year.

All patients are followed for up to 5 years post-randomization.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed biliary tract cancer (including intrahepatic or extrahepatic/hilar cholangiocarcinoma or muscle invasive gallbladder cancer or cancer of the distal bile duct)

• Must have undergone a radical surgical approach which includes liver resection, pancreatic resection, or less commonly both
• Patients with pathological evidence of microscopic involvement of the margins of the excised specimen are eligible as long as resection is macroscopically complete
• Must be able to start treatment within 12 weeks of surgery
• No pancreatic or periampullary cancer
• No mucosal gallbladder cancer

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Urea < 1.5 times upper limit of normal (ULN)
• Creatinine < 1.5 times ULN
• Glomerular filtration rate ≥ 60 mL/min (if < 60 mL/min, adequate renal function for capecitabine must be confirmed by isotope EDTA)
• Hemoglobin ≥ 10 g/dL
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 3 times ULN
• ALT and AST ≤ 5 times ULN
• Adequate surgical biliary drainage with no evidence of infection
• Not pregnant or nursing
• Negative pregnancy test for women of childbearing age and childbearing potential
• Fertile patients must use effective contraception during study treatment and for at least 3 months after study treatment has ended
• Must provide written informed consent
• No history of other malignant diseases within the past 5 years other than adequately treated nonmelanoma skin cancer or in situ carcinoma of the uterine cervix
• No serious co-existing medical condition likely to interfere with protocol treatment, including a potential serious infection
• No evidence of significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial
• No psychological, familial, sociological, or geographical factors considered likely to preclude study compliance
• No other serious uncontrolled medical conditions
• No unresolved biliary tree obstruction

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Completely recovered from prior surgery
• No use of other investigational agents within 28 days prior to and during study treatment
• No prior chemotherapy or radiotherapy for biliary tract cancer
• No other concurrent anticancer chemotherapy, radiotherapy, or investigational agent