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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving capecitabine after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether capecitabine is more effective than observation in treating biliary tract cancer. PURPOSE: This randomized phase III trial is studying capecitabine to see how well it works compared with observation in treating patients with biliary tract cancer.

Detailed Description
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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.

Official Title
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A Randomised Clinical Trial Evaluating Adjuvant Chemotherapy With Capecitabine Compared to Expectant Treatment Alone (Observation) Following Surgery for Biliary Tract Cancer

Conditions
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Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Liver Cancer

Intervention / Treatment
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* Drug: capecitabine
* Other: clinical observation
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|nan|
|Other: clinical observation|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 2 years |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 5 years |  |  | 
| Relapse-free survival |  |  | 
| Toxicity |  |  | 
| Quality of life |  |  | 
| Health economics |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized resectable adult primary liver cancer, cholangiocarcinoma of the extrahepatic bile duct, cholangiocarcinoma of the gallbladder, adenocarcinoma of the gallbladder, adenocarcinoma with squamous metaplasia of the gallbladder, anaplastic carcinoma of the gallbladder, localized gallbladder cancer, localized extrahepatic bile duct cancer, squamous cell carcinoma of the gallbladder, adult primary cholangiocellular carcinoma