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

NCT ID: NCT00303927

Last Updated: 2010-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31

Brief Summary

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

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.

Conditions

Pancreatic Cancer

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

capecitabine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Principal Investigators

Wells Messersmith, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Hospital Universitario 12 de Octubre

Madrid, , Spain

Countries

United States; Spain

Other Identifiers

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0560

Identifier Type: -

Identifier Source: secondary_id

JHOC-NA_00000937

Identifier Type: -

Identifier Source: secondary_id

CDR0000462118

Identifier Type: -

Identifier Source: org_study_id