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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01164215
Recruitment Status : Completed
First Posted : July 16, 2010
Last Update Posted : October 9, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Diarrhea Neutropenia Drug: fluorouracil Drug: leucovorin Drug: oxaliplatin Phase 1

Detailed Description:



  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter Study Investigating Utilization of Pharmacokinetic-Guided 5-Fluorouracil in Patients Receiving mFOLFOX6 With or Without Bevacizumab
Study Start Date : February 2010
Actual Primary Completion Date : November 2012
Actual Study Completion Date : September 2013

Arm Intervention/treatment
Experimental: mFOLFOX6

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)

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
Other Name: 5FU

Drug: leucovorin
200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks
Other Name: leucovorin calcium

Drug: oxaliplatin
85 mg/m2, intravenously for 2 hours, once every 2 weeks
Other Name: Eloxatin

Primary Outcome Measures :
  1. Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy [ Time Frame: During first 4 cycles of drug therapy ]

Secondary Outcome Measures :
  1. Toxicity differences between PK-guided therapy versus non-PK-guided therapy [ Time Frame: 24 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): 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
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Christine M. Walko, PharmD, BCOP UNC Lineberger Comprehensive Cancer Center

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: UNC Lineberger Comprehensive Cancer Center Identifier: NCT01164215     History of Changes
Other Study ID Numbers: LCCC 0918
P30CA016086 ( U.S. NIH Grant/Contract )
CDR0000681338 ( Other Identifier: PDQ number )
First Posted: July 16, 2010    Key Record Dates
Last Update Posted: October 9, 2015
Last Verified: October 2015

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
stage I colon cancer
stage II colon cancer
stage III colon cancer
stage IV colon cancer
recurrent colon cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Leukocyte Disorders
Hematologic Diseases
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs