Biomarker-Guided Fluorouracil in Treating Patients With Colorectal Cancer Receiving Combination Chemotherapy
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.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multicenter Study Investigating Utilization of Pharmacokinetic-Guided 5-Fluorouracil in Patients Receiving mFOLFOX6 With or Without Bevacizumab|
- Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy [ Time Frame: During first 4 cycles of drug therapy ] [ Designated as safety issue: No ]
- Toxicity differences between PK-guided therapy versus non-PK-guided therapy [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2010|
|Estimated Study Completion Date:||August 2015|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
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)
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
Other Name: 5FUDrug: leucovorin
200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks
Other Name: leucovorin calciumDrug: oxaliplatin
85 mg/m2, intravenously for 2 hours, once every 2 weeks
Other Name: Eloxatin
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01164215
|United States, North Carolina|
|Cancer Care of Western North Carolina|
|Asheville, North Carolina, United States, 28801|
|Moses Cone Regional Cancer Center at Wesley Long Community Hospital|
|Greensboro, North Carolina, United States, 27403-1198|
|Leo W. Jenkins Cancer Center at ECU Medical School|
|Greenville, North Carolina, United States, 27834|
|Rex Cancer Center at Rex Hospital|
|Raleigh, North Carolina, United States, 27607|
|Marion L. Shepard Cancer Center|
|Washington, North Carolina, United States, 27889|
|Principal Investigator:||Christine M. Walko, PharmD, BCOP||UNC Lineberger Comprehensive Cancer Center|