The Optimization of 5-Fluorouracil Dose by Pharmacokinetic Monitoring in Asian Patients With Advanced Stage Cancer

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

Verified September 2009 by National University Hospital, Singapore. Recruitment status was Recruiting

First Received on July 16, 2009. Last Updated on September 16, 2009 History of Changes

Sponsor:	National University Hospital, Singapore
Information provided by:	National University Hospital, Singapore
ClinicalTrials.gov Identifier:	NCT00943137

Purpose

The purpose of this study is:

To determine the proportion of Asian patients achieving a target area under the curve (AUC) of 20-24 mg.h/L using a pharmacokinetically guided 5-fluorouracil (5-FU) dose
To determine the safety and tolerability of dose adjusted 5-FU
To correlate 5-FU PK with gene variants associated with the 5-FU pathway and with clinical outcomes

Based on Western data, levels of 5-FU are highly variable when doses are based on BSA. A relationship between systemic plasma levels of 5-FU and treatment toxicity and efficacy exists. Whilst pharmacokinetically-guided dose management has been shown to improve 5-FU efficacy and tolerance, there is currently no data in Asian patients using this approach. Using pharmacokinetically guided 5-FU-dose adjustment, the investigators hypothesize the proportion of Asian patients achieving a target AUC of 20-24 mg.h/L is similar to that of Caucasians.

METHODS:

This is an open, non-randomised single center Phase II study evaluating dose adjusted 5-FU in patients receiving de Gramont, FOLFIRI or mFOLFOX-6 schedules.

Condition	Intervention	Phase
Advanced Stage Cancer	Drug: 5-Fluorouracil	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	The Optimisation of 5-Fluorouracil Dose by Pharmacokinetic Monitoring in Asian Patients With Advanced Stage Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Fluorouracil

U.S. FDA Resources

Further study details as provided by National University Hospital, Singapore:

Estimated Enrollment:	55
Study Start Date:	June 2009

Eligibility

Ages Eligible for Study:	21 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients aged = 21 years to 80 years
Histologically proven advanced stage carcinoma where De Gramont, FOLFIRI or mFOLFOX-6 regimen is indicated.
No more than one line of prior chemotherapy for advanced stage disease
Measurable disease according to RECIST criteria or evaluable disease
Kanorfsky performance status of at least 70% or ECOG performance status ? 2
A life expectancy of at least 3 months
ANC > 1.5 x 10^9/L
Platelet count > 100 x 10^9/L.
Total bilirubin > 1.5x upper limits of normal reference range (ULN)
AST/ALT levels > 2.5x upper limit of normal. If hepatic metastases are present, these parameters could be ? 5x the ULN.
Women of reproductive age and men must agree to practice effective contraception during the entire study period. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-child-bearing potential. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrolment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Signed informed consent

Exclusion Criteria:

Received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic or any investigational therapy within 21 days prior to study drug administration (6 weeks for mitomycin or nitroureas) and have not recovered from therapy.
Patients who have not recovered from major surgery
Subjects with treated brain metastases are eligible provided they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to study drug administration).
Clinically significant cardiac disease, eg. myocardial infarction within the last 12 months.
Known HIV infection
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, other serious uncontrolled concomitant disease, psychiatric illness/ social situation that would limit study compliance.
Known allergies to any component of the drug regime
Organ allografts
Known dihydropyrimidine dehydrogenase deficiency

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943137

Contacts

Contact: Wei Peng Yong, MRCP, MB ChB

65 6772 4670

Wei_Peng_Yong@nuhs.edu.sg

Locations

Singapore
National University Hospital	Recruiting
Singapore, Singapore, 119074
Contact: Wei Peng Yong, MRCP, MB ChB 65 6772 4670 Wei_Peng_Yong@nuhs.edu.sg
Principal Investigator: Wei Peng Yong, MRCP, MB ChB

Sponsors and Collaborators

National University Hospital, Singapore

Investigators

Principal Investigator:

Wei Peng Yong, MRCP, MB ChB

National University Hospital, Singapore

More Information

Publications:

[No authors listed] Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. Meta-analysis Group In Cancer. J Clin Oncol. 1998 Jan;16(1):301-8.

[No authors listed] Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. Meta-Analysis Group In Cancer. J Clin Oncol. 1998 Nov;16(11):3537-41.

ClinicalTrials.gov Identifier:	NCT00943137 History of Changes
Other Study ID Numbers:	PK01/06/09
Study First Received:	July 16, 2009
Last Updated:	September 16, 2009
Health Authority:	Singapore: Domain Specific Review Boards

Additional relevant MeSH terms:

Fluorouracil
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic

Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012