Capecitabine as Second-Line Therapy in Treating Patients With Stage IV Pancreatic Cancer Who Have the Thymidylate Synthase Gene

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. PURPOSE: This phase II trial is studying how well capecitabine works as second-line therapy in treating patients with stage IV pancreatic cancer who have the thymidylate synthase gene.

Detailed Description
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OBJECTIVES: Primary Characterize the 6-month survival of patients with stage IV pancreatic cancer (progressing after at least 1 prior gemcitabine-containing chemotherapy regimen) who carry the double tandem repeat (S/S) variant of the thymidylate synthase (TS) gene enhancer region (TSER) treated with capecitabine. Characterize toxicity of capecitabine in patients with stage IV pancreatic cancer who carry the S/S variant of the TSER. Secondary Explore the association between capecitabine exposure at steady-state, allelic variants in candidate genes (carboxylesterase 1, carboxylesterase 2, cytidine deaminase, thymidine phosphorylase [TP], dihydropyrimidine dehydrogenase [DPD], methylenetetrahydrofolate reductase) and drug response (toxicity and efficacy) in this patient population. Determine the relationship between expression of TS, TP, and DPD in tumor tissues and the response to capecitabine in this patient population. Analyze response rate to capecitabine, based on the presence of homozygous S/S variant of the TSER. OUTLINE: This is an open-label, multicenter study. Patients receive oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.

Official Title
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Thymidylate Synthase (TS) Genotype-Directed Phase II Trial of Oral Capecitabine for 2-Line Treatment of Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: capecitabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed pancreatic cancer Stage IV disease Measurable disease (≥ 1 cm or > 10 mm lesion(s) by spiral CT scan) Disease progression after ≥ 1 gemcitabine-based treatment regimen for advanced/metastatic disease Patient carries the double tandem repeat (S/S) variant of the thymidylate synthase gene enhancer region (TSER) No active CNS metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive growth) PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 AST/ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if attributable to liver metastases) Total bilirubin ≤ 1.5 times ULN Creatinine normal OR creatinine clearance > 50 mL/min Fertile patients must use effective contraception during and for 30 days after completion of study treatment Not pregnant or nursing Negative pregnancy test Asymptomatic HIV infection allowed No recent or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, bleeding, inflammation, emesis, or diarrhea > grade 1) Able to swallow capecitabine tablets No known hypersensitivity to fluorouracil No dihydropyrimidine dehydrogenase (DPD) deficiency No clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmias not well controlled with medication) No myocardial infarction within the past 6 months No serious, uncontrolled, concurrent infection(s) No prior unanticipated severe reaction to fluoropyrimidine therapy No other malignancy within the past 5 years except cured nonmelanoma skin cancer or treated carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 3 weeks since prior chemotherapy No prior capecitabine except in the adjuvant setting At least 3 weeks since prior radiotherapy or major surgery At least 4 weeks since prior participation in any investigational drug study At least 4 weeks since prior sorivudine or brivudine No concurrent sorivudine or brivudine No concurrent cimetidine or azidothymidine (AZT) Concurrent radiotherapy for bone pain allowed to a limited field provided ≥ 1 indicator lesion remains outside of the field No other concurrent chemotherapy or immunotherapy

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 6-months |  |  | 
| Toxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between capecitabine exposure at steady-state, allelic variants in candidate genes, and drug response |  |  | 
| Relationship between expression of TS, TP and DPD in tumor tissues and response |  |  | 
| Response rate |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent pancreatic cancer, stage IV pancreatic cancer