Adjuvant Palliative Capecitabine and Gemcitabine in Treating Patients With Locally Advanced or Metastatic Biliary Tract Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as capecitabine and gemcitabine, use different ways to stop tumor cells from dividing so they stop growing or die. Palliative chemotherapy may improve the quality of life in patients who have locally advanced or metastatic biliary tract cancer and may help them live more comfortably. PURPOSE: Phase II trial to study the effectiveness of adjuvant capecitabine and gemcitabine in improving quality of life in patients who have locally advanced or metastatic biliary tract cancer.

Detailed Description
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OBJECTIVES: Primary Determine the ability of palliative capecitabine and gemcitabine to maintain or improve tumor-related symptoms (after treatable biliary duct obstruction has been relieved) as measured by the clinical benefit response in patients with locally advanced or metastatic biliary tract cancer. Secondary Determine the clinical benefit response in patients treated with this regimen. Determine the time to and duration of clinical benefit response in patients treated with this regimen. Determine the objective response and time to progression in patients treated with this regimen. Determine the overall survival of patients treated with this regimen. Determine the quality of life of patients treated with this regimen. Determine the adverse events in patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and oral capecitabine twice daily on days 1-14 (28 total doses). Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients responding to treatment may receive additional courses at the discretion of the investigator. Quality of life is assessed at baseline, weekly during weeks 2-9 (courses 1-3), and then before each administration of gemcitabine. Patients are followed every 3 months for 1 year and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 19-44 patients will be accrued for this study within 3 years.

Official Title
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Capecitabine And Gemcitabine In Patients With Advanced Or Metastatic Biliary Tract Cancer, A Multicenter Phase II Trial

Conditions
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Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Liver Cancer, Pain

Intervention / Treatment
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* Drug: capecitabine plus gemcitabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed biliary tract cancer Locally advanced, unresectable, or metastatic disease Metastatic adenocarcinoma with clinical documentation of gallbladder or bile tree involvement with no evidence of another primary adenocarcinoma allowed Measurable or nonmeasurable disease Treatable biliary duct obstruction must be relieved by either internal endoscopic drainage/stenting or palliative bypass surgery before study entry Symptomatic biliary tract cancer and has at least 1 of the following: Karnofsky 60-80% Baseline analgesic consumption at least 10 mg of morphine equivalents per day Baseline pain intensity score of at least 20 mm out of a possible 100 mm No prior or concurrent CNS metastasis PATIENT CHARACTERISTICS: Age 18 to 80 Performance status See Disease Characteristics Karnofsky 60-100% Life expectancy Not specified Hematopoietic Neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL Hepatic Bilirubin no greater than 4 times upper limit of normal (ULN) Alkaline phosphatase no greater than 5 times ULN AST and ALT no greater than 5 times ULN Renal Creatinine clearance greater than 50 mL/min Cardiovascular No uncontrolled cardiovascular disease Gastrointestinal Able to ingest oral medication No malabsorption syndrome No intractable nausea and/or vomiting No partial small bowel obstruction Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 year after study participation No active autoimmune disease No uncontrolled diabetes No known hypersensitivity to fluorouracil No known dihydropyrimidine dehydrogenase deficiency No definitive contraindication to corticosteroids No prior significant neurologic or psychiatric disorders (e.g., psychotic disorders, dementia, or seizures) that would preclude understanding or providing informed consent No prior severe reaction to fluoropyrimidine therapy No psychiatric disorder, cognitive dysfunction, or language problem that would preclude filling out the quality of life questionnaire or patient diary No other serious underlying medical condition that would preclude study participation No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy No prior biologic therapy No prior immunotherapy Chemotherapy No prior chemotherapy for advanced/metastatic disease No prior palliative chemotherapy Endocrine therapy No concurrent megestrol Radiotherapy More than 4 weeks since prior radiotherapy No concurrent radiotherapy Treatment of a single painful lesion allowed Surgery See Disease Characteristics Prior Whipple procedure allowed Prior duodenal bypass allowed No concurrent endoscopic or external biliary drainage as a consequence of progressive malignant bile duct obstruction Drainage as a consequence of nonmalignant bile duct obstruction allowed Other More than 30 days since prior treatment within a clinical study No other concurrent anticancer drugs No other concurrent investigational drugs No concurrent sorivudine or its chemically-related analogues (e.g., lamivudine)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Capecitabine plus Gemcitabine | Drug: capecitabine plus gemcitabine<br>* capecitabine plus gemcitabine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability of palliative capecitabine and gemcitabine | Determine the ability of palliative capecitabine and gemcitabine to maintain or improve tumor-related symptoms (after treatable biliary duct obstruction has been relieved) as measured by the clinical benefit response. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit response alone as measured after 3 courses |  | 3 months | 

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