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

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00303927

Purpose

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.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: capecitabine	Phase II

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Capecitabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Thymidylate Synthase (TS) Genotype-Directed Phase II Trial of Oral Capecitabine for 2-Line Treatment of Advanced Pancreatic Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Survival at 6-months [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Association between capecitabine exposure at steady-state, allelic variants in candidate genes, and drug response [ Designated as safety issue: No ]
Relationship between expression of TS, TP and DPD in tumor tissues and response [ Designated as safety issue: No ]
Response rate [ Designated as safety issue: No ]

Estimated Enrollment:	65
Study Start Date:	December 2005
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303927

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Spain
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Wells Messersmith, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000462118, JHOC-J0560, JHOC-NA_00000937
Study First Received:	March 15, 2006
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00303927
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent pancreatic cancer
stage IV pancreatic cancer

Study placed in the following topic categories:

Capecitabine
Digestive System Diseases
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases

Pancreatic Diseases
Gastrointestinal Neoplasms
Endocrinopathy
Recurrence
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009