search
Back to results

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

Primary Purpose

Colorectal Cancer, Diarrhea, Neutropenia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fluorouracil
leucovorin
oxaliplatin
Sponsored by
UNC Lineberger Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring neutropenia, diarrhea, 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

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cancer Care of Western North Carolina
  • Moses Cone Regional Cancer Center at Wesley Long Community Hospital
  • Leo W. Jenkins Cancer Center at ECU Medical School
  • Rex Cancer Center at Rex Hospital
  • Marion L. Shepard Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

mFOLFOX6

Arm Description

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)

Outcomes

Primary Outcome Measures

Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy

Secondary Outcome Measures

Toxicity differences between PK-guided therapy versus non-PK-guided therapy

Full Information

First Posted
July 15, 2010
Last Updated
October 7, 2015
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01164215
Brief Title
Biomarker-Guided Fluorouracil in Treating Patients With Colorectal Cancer Receiving Combination Chemotherapy
Official Title
Multicenter Study Investigating Utilization of Pharmacokinetic-Guided 5-Fluorouracil in Patients Receiving mFOLFOX6 With or Without Bevacizumab
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Diarrhea, Neutropenia
Keywords
neutropenia, diarrhea, 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
mFOLFOX6
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
5FU
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
leucovorin
Other Intervention Name(s)
leucovorin calcium
Intervention Description
200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
85 mg/m2, intravenously for 2 hours, once every 2 weeks
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Toxicity differences between PK-guided therapy versus non-PK-guided therapy
Time Frame
24 months

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christine M. Walko, PharmD, BCOP
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer Care of Western North Carolina
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Moses Cone Regional Cancer Center at Wesley Long Community Hospital
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27403-1198
Country
United States
Facility Name
Leo W. Jenkins Cancer Center at ECU Medical School
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Rex Cancer Center at Rex Hospital
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Marion L. Shepard Cancer Center
City
Washington
State/Province
North Carolina
ZIP/Postal Code
27889
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29159476
Citation
Williams GR, Deal AM, Shachar SS, Walko CM, Patel JN, O'Neil B, McLeod HL, Weinberg MS, Choi SK, Muss HB, Sanoff HK. The impact of skeletal muscle on the pharmacokinetics and toxicity of 5-fluorouracil in colorectal cancer. Cancer Chemother Pharmacol. 2018 Feb;81(2):413-417. doi: 10.1007/s00280-017-3487-2. Epub 2017 Nov 20.
Results Reference
derived
PubMed Identifier
25117066
Citation
Patel JN, O'Neil BH, Deal AM, Ibrahim JG, Sherrill GB, Olajide OA, Atluri PM, Inzerillo JJ, Chay CH, McLeod HL, Walko CM. A community-based multicenter trial of pharmacokinetically guided 5-fluorouracil dosing for personalized colorectal cancer therapy. Oncologist. 2014 Sep;19(9):959-65. doi: 10.1634/theoncologist.2014-0132. Epub 2014 Aug 12.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs