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

Phase 1

Completed

• Conditions: Diarrhea; Neutropenia; Colorectal Cancer
• Interventions: Drug: fluorouracil; Drug: leucovorin; Drug: oxaliplatin

• Registration Number: NCT01164215
• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2010-02
• Study First Submitted: 2010-07-15
• Study First Submitted QC: 2010-07-15
• Study First Posted: 2010-07-16
• Primary Completion: 2012-11
• Study Completion: 2013-09
• Status Verified: 2015-10
• Last Update Submitted: 2015-10-07
• Last Update Posted: 2015-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
mFOLFOX6	leucovorin	Patients will receive cycle 1 of standard dose mFOLFOX6, with the same dose of mFOLFOX6 continued in subsequent cycles, once patient achieves the target AUC. mFOLFOX 6 is a regimen comprised of Oxaliplatin + Leucovorin +5-Fluorouracil (FU)
mFOLFOX6	oxaliplatin	Patients will receive cycle 1 of standard dose mFOLFOX6, with the same dose of mFOLFOX6 continued in subsequent cycles, once patient achieves the target AUC. mFOLFOX 6 is a regimen comprised of Oxaliplatin + Leucovorin +5-Fluorouracil (FU)
mFOLFOX6	fluorouracil	Patients will receive cycle 1 of standard dose mFOLFOX6, with the same dose of mFOLFOX6 continued in subsequent cycles, once patient achieves the target AUC. mFOLFOX 6 is a regimen comprised of Oxaliplatin + Leucovorin +5-Fluorouracil (FU)

Primary Outcome Measures

Name	Time	Method
Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy	During first 4 cycles of drug therapy

Secondary Outcome Measures

Name	Time	Method
Toxicity differences between PK-guided therapy versus non-PK-guided therapy	24 months

Trial Locations

Locations (5)

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, United States