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

NCT00943137 | Unknown Phase 2

• 1 other identifier: PK01/06/09
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is:

1. 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. 2.To determine the safety and tolerability of dose adjusted 5-FU
3. 3.To correlate 5-FU pharmacokinetics with gene variants associated with the 5-FU pathway and with clinical outcomes

Conditions

Cancer (Advanced Stage)

Outcome Measures

Primary Outcomes (1)

• AUC of 20-24 mg.h/L

  If patient achieved target AUC for two consecutive cycles, therapeutic dose monitoring will performed every alternate cycle.

  28 days - 2 cycles

Study Arms (1)

5-FU dosage adjustments

EXPERIMENTAL

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

Interventions

5-Fluorouracil DRUG

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.

5-FU dosage adjustments

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, 119074, Singapore

Location

Related Publications (2)

• Meta-analysis Group In Cancer; Piedbois P, Rougier P, Buyse M, Pignon J, Ryan L, Hansen R, Zee B, Weinerman B, Pater J, Leichman C, Macdonald J, Benedetti J, Lokich J, Fryer J, Brufman G, Isacson R, Laplanche A, Levy E. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol. 1998 Jan;16(1):301-8. doi: 10.1200/JCO.1998.16.1.301.

  PMID: 9440757 BACKGROUND

• Meta-Analysis Group In Cancer; Levy E, Piedbois P, Buyse M, Pignon JP, Rougier P, Ryan L, Hansen R, Zee B, Weinerman B, Pater J, Leichman C, Macdonald J, Benedetti J, Lokich J, Fryer J, Brufman G, Isacson R, Laplanche A, Quinaux E, Thirion P. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol. 1998 Nov;16(11):3537-41. doi: 10.1200/JCO.1998.16.11.3537.

  PMID: 9817272 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

Fluorouracil

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Thomas Soh, MBBS

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2009
• First Posted: July 22, 2009
• Study Start: June 1, 2009
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2017
• Last Updated: June 19, 2015

Record last verified: 2015-06

Locations

SG (1)