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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00303927
• Other study ID #: CDR0000462118
• Secondary ID: P30CA006973JHOC-
• Status: Completed
• Phase: Phase 2
• First received: March 15, 2006
• Last updated: March 18, 2010
• Start date: December 2005

Study information

• Verified date: March 2010
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• capecitabine

Locations

Country	Name	City	State
Spain	Hospital Universitario 12 de Octubre	Madrid
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival at 6-months			No
Primary	Toxicity			Yes
Secondary	Association between capecitabine exposure at steady-state, allelic variants in candidate genes, and drug response			No
Secondary	Relationship between expression of TS, TP and DPD in tumor tissues and response			No
Secondary	Response rate			No