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

March 3, 2014 updated by: The Netherlands Cancer Institute
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1066CX
        • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
      • Amsterdam, Netherlands, 1066
        • Slotervaart Hospital
      • Nijmegen, Netherlands, 6532SZ
        • Canisius Wilhelmina Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • 5-FU
  • Xeloda
  • Capecitabine
  • 5-Fluorouracil
  • Fluorouracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
safety
Time Frame: during fluoropyrimidine treatment of the patient
during fluoropyrimidine treatment of the patient

Secondary Outcome Measures

Outcome Measure
Time Frame
cost-effectiveness
Time Frame: during fluoropyrimidine treatment of the patient
during fluoropyrimidine treatment of the patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Netherlands Cancer Institute

Investigators

  • Principal Investigator: Jan HM Schellens, MD, PhD, Netherlands Cancer Institute, Amsterdam, the Netherlands

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

October 1, 2011

Study Completion (Actual)

October 1, 2011

Study Registration Dates

First Submitted

February 5, 2009

First Submitted That Met QC Criteria

February 5, 2009

First Posted (Estimate)

February 6, 2009

Study Record Updates

Last Update Posted (Estimate)

March 4, 2014

Last Update Submitted That Met QC Criteria

March 3, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NKI-AVL_M07PFU

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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