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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00838370
• Other study ID #: NKI-AVL_M07PFU
• Status: Completed
• Phase: Phase 1
• First received: February 5, 2009
• Last updated: March 3, 2014
• Start date: May 2007
• Est. completion date: October 2011

Study information

• Verified date: March 2014
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	Slotervaart Hospital	Amsterdam
Netherlands	Canisius Wilhelmina Hospital	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	safety		during fluoropyrimidine treatment of the patient	Yes
Secondary	cost-effectiveness		during fluoropyrimidine treatment of the patient	No