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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT00943137
First received: July 16, 2009
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Cancer (Advanced Stage)
Drug: 5-Fluorouracil
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
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:


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

Primary Outcome Measures:
  • AUC of 20-24 mg.h/L [ Time Frame: 28 days - 2 cycles ] [ Designated as safety issue: No ]
    If patient achieved target AUC for two consecutive cycles, therapeutic dose monitoring will performed every alternate cycle.


Estimated Enrollment: 55
Study Start Date: June 2009
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Singapore
National University Hospital
Singapore, Singapore, 119074
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Thomas Soh, MBBS National University Hospital, Singapore
  More Information

Publications:
Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT00943137     History of Changes
Other Study ID Numbers: PK01/06/09
Study First Received: July 16, 2009
Last Updated: December 10, 2013
Health Authority: Singapore: Domain Specific Review Boards

Additional relevant MeSH terms:
Fluorouracil
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014