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

The recruitment status of this study is unknown because the information has not been verified recently.

Verified July 2010 by The Netherlands Cancer Institute.
Recruitment status was Recruiting

Sponsor:

Information provided by:

The Netherlands Cancer Institute

ClinicalTrials.gov Identifier:

NCT00838370

First received: February 5, 2009

Last updated: July 29, 2010

Last verified: July 2010

History of Changes

Tracking Information

First Received Date ^ICMJE

February 5, 2009

Last Updated Date

July 29, 2010

Start Date ^ICMJE

May 2007

Estimated Primary Completion Date

July 2009 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT00838370 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief 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.

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.

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

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

Condition ^ICMJE

Neoplasms

Intervention ^ICMJE

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

Study Arm (s)

Experimental: DPYD*2A

Intervention: Drug: Capecitabine, 5-fluorouracil

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

August 2009

Estimated Primary Completion Date

July 2009 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Jan HM Schellens, MD, PhD

0031205122446

j.slijkerman@nki.nl

Location Countries ^ICMJE

Netherlands

Administrative Information

NCT Number ^ICMJE

NCT00838370

Other Study ID Numbers ^ICMJE

NKI-AVL_M07PFU

Has Data Monitoring Committee

Yes

Responsible Party

Prof. dr. J.H.M. Schellens, The Netherlands Cancer Institute

Study Sponsor ^ICMJE

The Netherlands Cancer Institute

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:

Jan HM Schellens, MD, PhD

Netherlands Cancer Institute, Amsterdam, the Netherlands

Information Provided By

The Netherlands Cancer Institute

Verification Date

July 2010

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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