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

June 17, 2015 updated by: National University Hospital, Singapore

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

The purpose of this study is:

  1. 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
  2. To determine the safety and tolerability of dose adjusted 5-FU
  3. 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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

55

Phase

  • Phase 2

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

  • Singapore
      • Singapore, Singapore, 119074
        • National University 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

21 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 5-FU dosage adjustments
The dose of continuous infusion 5-FU will be adjusted every cycle until patients reached the therapeutic plasma range (450 to 550 microgram/L).
Drug: 5-Fluorouracil

Chemotherapy will be one of the following:

  1. de Gramont: folinic acid 400mg/m2 day 1, 5-FU 400 mg/m2 bolus on day 1 followed by 46 hour continuous infusion of 5-FU 2400mg/m2.
  2. FOLFIRI: Irinotecan 180mg/m2 on day 1, folinic acid 400mg/m2 day 1, 5-FU 400 mg/m2 bolus on day 1 followed by 46 hour continuous infusion of 5-FU 2400mg/m2.
  3. Modified FOLFOX-6: Oxaliplatin 85mg/m2 on day 1, folinic acid 400mg/m2 day 1, 5-FU 400 mg/m2 bolus on day 1 followed by 46 hour continuous infusion of 5-FU 2400mg/m2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC of 20-24 mg.h/L
Time Frame: 28 days - 2 cycles
If patient achieved target AUC for two consecutive cycles, therapeutic dose monitoring will performed every alternate cycle.
28 days - 2 cycles

Collaborators and Investigators

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

Sponsor

National University Hospital, Singapore

Investigators

  • Principal Investigator: Thomas Soh, MBBS, National University Hospital, Singapore

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

June 1, 2009

Primary Completion (Anticipated)

June 1, 2016

Study Completion (Anticipated)

June 1, 2017

Study Registration Dates

First Submitted

July 16, 2009

First Submitted That Met QC Criteria

July 21, 2009

First Posted (Estimate)

July 22, 2009

Study Record Updates

Last Update Posted (Estimate)

June 19, 2015

Last Update Submitted That Met QC Criteria

June 17, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PK01/06/09

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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