Capecitabine As Second-Line Therapy In Treating Patients With Stage IV Pancreatic Cancer Who Have The Thymidylate Synthase Gene

Study Overview

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

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.

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.

Pancreatic Cancer

DRUG: capecitabine

CDR0000462118
P30CA006973 (U.S. NIH Grant/Contract)
JHOC-J0560
JHOC-NA_00000937

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2006-03-15	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2010-03-18
First Submitted that Met QC Criteria 2006-03-15	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2010-03-19
First Posted (ESTIMATED) 2006-03-17	Results First Posted N/A	Last Verified 2010-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
N/A

Interventional Model:
N/A

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
Survival at 6-months
Toxicity

Secondary Outcome Measures	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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)

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: Wells Messersmith, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

Patients

Caregivers

Clinical Trial Record