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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00303927
First received: March 15, 2006
Last updated: March 18, 2010
Last verified: March 2010
  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 2

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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

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
Investigators
Study Chair: Wells Messersmith, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Wells Messersmith, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00303927     History of Changes
Other Study ID Numbers: CDR0000462118, P30CA006973, JHOC-J0560, JHOC-NA_00000937
Study First Received: March 15, 2006
Last Updated: March 18, 2010
Health Authority: United States: Federal Government

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
recurrent pancreatic cancer
stage IV pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 15, 2014