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

National University Health System (NUHS)

Status and phase

Unknown

Phase 2

Conditions

Cancer (Advanced Stage)

Treatments

Drug: 5-Fluorouracil

Study type

Interventional

Funder types

Other

Identifiers

NCT00943137

PK01/06/09

Details and patient eligibility

About

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 pharmacokinetics 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.

Enrollment

55 estimated patients

Sex

All

Ages

21 to 80 years old

Volunteers

No Healthy Volunteers

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
Karnofsky performance status of at least 70% or electrocorticogram performance status ? 2
A life expectancy of at least 3 months
absolute neutrophil count > 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 enrollment. 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, e.g. 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