Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines

This study has been completed.
Sponsor:
Information provided by:
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT00838370
First received: February 5, 2009
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

The primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD*2A, and to determine whether this strategy is cost-effective. Secondly, an individualized treatment algorithm for capecitabine and 5-FU therapy in DPYD*2A mutant patients will be developed and the pharmacokinetic profile of capecitabine and 5-FU will be assessed.


Condition Intervention Phase
Neoplasms
Drug: Capecitabine, 5-fluorouracil
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines

Resource links provided by NLM:


Further study details as provided by The Netherlands Cancer Institute:

Primary Outcome Measures:
  • safety [ Time Frame: during fluoropyrimidine treatment of the patient ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • cost-effectiveness [ Time Frame: during fluoropyrimidine treatment of the patient ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: May 2007
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DPYD*2A
Patients are screened for a DPD-deficiency. Patients with a DPYD*2A mutation are eligible for intervention with capecitabine/5-FU .
Drug: Capecitabine, 5-fluorouracil

Patients to treat with capecitabine/5-FU will be screened prior to start of therapy for DPYD*2A. Patients heterozygous or homozygous mutant for DPYD*2A receive dose reductions of capecitabine/5-FU of at least 50% in the first two courses. In case this dose is tolerated well, doses will be increased.

In addition, the pharmacokinetics of capecitabine/5-FU and their metabolites will be assessed in these patients.

Other Names:
  • Xeloda
  • Capecitabine
  • Fluorouracil
  • 5-Fluorouracil
  • 5-FU

Detailed Description:

Patients exhibiting a genetically determined disorder (DPYD*2A) in the metabolic degradation of the frequently used anticancer agents capecitabine and 5-FU (fluoropyrimidines) are at high risk of development of severe and life-threatening toxicity during standard treatment with these compounds. Treatment and recovery of this fluoropyrimidine-induced severe toxicity often requires prolonged periods of hospitalization.

Screening for DPYD*2A in patients to treat with fluoropyrimidine drugs with subsequent dose adjustments in mutant individuals prior to start of therapy will possibly reduce the number of severe toxicity events. Furthermore, by reducing the frequency and/or duration of hospitalization, substantial medical costs can be saved, making this a cost-effective strategy.

  Eligibility

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

Inclusion Criteria:

  • Histological proof of cancer
  • patient is considered for treatment with capecitabine or 5-FU
  • hetero- or homozygous mutant for DPYD*2A
  • able and willing to give written informed consent
  • able and willing to undergo blood sampling for pharmacokinetic analysis
  • life expectancy 3 months or longer
  • acceptable safety laboratory values (ANC, platelet count, ASAT, ALAT, creatinine,
  • WHO performance status 0-2
  • no radio- or chemotherapy within the last 3 weeks prior to study entry

Exclusion Criteria:

  • patients with known alcoholism, drug addiction and/or psychotic disorders that are not suitable for adequate follow-up
  • women who are pregnant or breast-feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00838370

Locations
Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands, 1066CX
Slotervaart Hospital
Amsterdam, Netherlands, 1066
Canisius Wilhelmina Hospital
Nijmegen, Netherlands, 6532SZ
Sponsors and Collaborators
The Netherlands Cancer Institute
Investigators
Principal Investigator: Jan HM Schellens, MD, PhD Netherlands Cancer Institute, Amsterdam, the Netherlands
  More Information

No publications provided

Responsible Party: Prof. dr. J.H.M. Schellens, The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT00838370     History of Changes
Other Study ID Numbers: NKI-AVL_M07PFU
Study First Received: February 5, 2009
Last Updated: March 3, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by The Netherlands Cancer Institute:
Pharmacogenetics
cost-benefit analysis
toxicity
antineoplastic drugs
Dihydropyrimidine Dehydrogenase

Additional relevant MeSH terms:
Neoplasms
Capecitabine
Antineoplastic Agents
Fluorouracil
Dihydrouracil Dehydrogenase (NADP)
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014