Biomarker-Guided Fluorouracil in Treating Patients With Colorectal Cancer Receiving Combination Chemotherapy

Colorectal Cancer Clinical Trial

Official title:

Multicenter Study Investigating Utilization of Pharmacokinetic-Guided 5-Fluorouracil in Patients Receiving mFOLFOX6 With or Without Bevacizumab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01164215
• Other study ID #: LCCC 0918
• Secondary ID: P30CA016086CDR00
• Status: Completed
• Phase: Phase 1
• First received: July 15, 2010
• Last updated: October 7, 2015
• Start date: February 2010
• Est. completion date: September 2013

Study information

• Verified date: October 2015
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug, combination chemotherapy, may kill more tumor cells. Studying samples of blood in the laboratory from patients with cancer receiving fluorouracil in combination with oxaliplatin and leucovorin calcium may help doctors learn how fluorouracil works in the body and how patients will respond to treatment.

PURPOSE: This phase I trial is studying biomarker-guided fluorouracil in treating patients with colorectal cancer receiving combination chemotherapy.

Description:

OBJECTIVES:

Primary

• To determine whether 4 courses of pharmacokinetic (PK)-guided 5-fluorouracil chemotherapy improves the ability to achieve a targeted area under the curve (20 to 25 mg*hr/L) in patients with colorectal cancer receiving mFOLFOX6 chemotherapy as compared to historical non-PK-guided therapy in patients treated with a similar FOLFOX regimen.

Secondary

• To determine and compare the incidence of neutropenia and diarrhea in patients treated with these regimens.

OUTLINE: This is a multicenter study.

• Standard mFOLFOX6 (course 1): Patients receive fluorouracil IV bolus over 1-5 minutes followed by fluorouracil IV continuously over 46 hours, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1.

Patients undergo plasma sample collection periodically during study for pharmacokinetic (PK)-guided fluorouracil dose determination for courses 2-4.

• PK-guided mFOLFOX6 (courses 2-4): Patients receive fluorouracil bolus, oxaliplatin, and leucovorin calcium as in course 1. Patients also receive fluorouracil* IV continuously as determined by the PK-guided analysis.

NOTE: *The continuous infusion fluorouracil dose adjustment is calculated based on the results of PK plasma concentrations and the corresponding AUC from the preceding course.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: September 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Patients scheduled to receive mFOLFOX6 (in the adjuvant setting or for metastatic disease) as part of their chemotherapy regimen

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy > 6 months

• ANC = 1,500/mm³

• Platelet count = 100,000/mm³

• Serum creatinine = 1.5 mg/dL

• Total bilirubin = 1.5 times upper limit of normal (ULN)

• AST and ALT = 2.5 times ULN (= 5 times ULN in the presence of liver metastases)

• Fertile patients must use effective contraception

• Negative pregnancy test

• Not pregnant or nursing

• No serious concomitant systemic disorders, including active infection that, in the opinion of the investigator, would compromise the patient's safety or ability to complete the study

• No altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies

• Must be able to follow protocol requirements and give informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Concurrent bevacizumab allowed

• No concurrent warfarin (Coumadin®)

• Concurrent enoxaparin (Lovenox®) allowed

• No concurrent theophylline or aminophylline

• No chocolate beginning 12 hours before day 1 of each course and through the end of that course's fluorouracil continuous IV

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Diarrhea
• Neutropenia

Intervention

Drug:
• fluorouracil
200-400 mg/m2 intravenously, 1 -5 minutes, once every 2 weeks 2400 mg/m2 intravenously over a period of 46 hours, once every 2 weeks
• leucovorin
200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks
• oxaliplatin
85 mg/m2, intravenously for 2 hours, once every 2 weeks

Locations

Country	Name	City	State
United States	Cancer Care of Western North Carolina	Asheville	North Carolina
United States	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina
United States	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina
United States	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina
United States	Marion L. Shepard Cancer Center	Washington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy		During first 4 cycles of drug therapy	No
Secondary	Toxicity differences between PK-guided therapy versus non-PK-guided therapy		24 months	Yes