Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
Recruitment status was Recruiting
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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 |
- safety [ Time Frame: during fluoropyrimidine treatment of the patient ] [ Designated as safety issue: Yes ]
- cost-effectiveness [ Time Frame: during fluoropyrimidine treatment of the patient ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 10 |
| Study Start Date: | May 2007 |
| Estimated Study Completion Date: | August 2009 |
| Estimated Primary Completion Date: | July 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: DPYD*2A |
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:
|
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 |
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| Contact: Jan HM Schellens, MD, PhD | 0031205122446 | j.slijkerman@nki.nl |
| Netherlands | |
| Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital | Recruiting |
| Amsterdam, Netherlands, 1066CX | |
| Contact: Jan HM Schellens, MD, PhD j.slijkerman@nki.nl | |
| Principal Investigator: Jan HM Schellens, MD, PhD | |
| Slotervaart Hospital | Recruiting |
| Amsterdam, Netherlands, 1066 | |
| Contact: marcel soesan, MD, PhD 0031205129333 | |
| Principal Investigator: Marcel Soesan, MD, PhD | |
| Canisius Wilhelmina Hospital | Recruiting |
| Nijmegen, Netherlands, 6532SZ | |
| Contact: Caroline Mandigers, MD, PhD c.mandigers@cwz.nl | |
| Principal Investigator: Caroline Mandigers, MD, PhD | |
| 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: | July 29, 2010 |
| 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 May 23, 2013