Biomarker-Guided Fluorouracil in Treating Patients With Colorectal Cancer Receiving Combination Chemotherapy
This study is ongoing, but not recruiting participants.
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01164215
First received: July 15, 2010
Last updated: February 1, 2013
Last verified: January 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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 | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer Diarrhea Neutropenia |
Drug: fluorouracil Drug: leucovorin Drug: oxaliplatin |
Phase 1 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Further study details as provided by UNC Lineberger Comprehensive Cancer Center:
Primary Outcome Measures:
- 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 ]
Secondary Outcome Measures:
- Toxicity differences between PK-guided therapy versus non-PK-guided therapy [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
| Enrollment: | 76 |
| Study Start Date: | February 2010 |
| Estimated Study Completion Date: | August 2015 |
| Primary Completion Date: | November 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
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.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01164215
Locations
| 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
Investigators
| Principal Investigator: | Christine M. Walko, PharmD, BCOP | UNC Lineberger Comprehensive Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | UNC Lineberger Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01164215 History of Changes |
| Other Study ID Numbers: | LCCC 0918, P30CA016086, CDR0000681338 |
| Study First Received: | July 15, 2010 |
| Last Updated: | February 1, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
|
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 |
Additional relevant MeSH terms:
|
Colorectal Neoplasms Diarrhea Neutropenia Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Signs and Symptoms, Digestive Signs and Symptoms |
Agranulocytosis Leukopenia Leukocyte Disorders Hematologic Diseases Fluorouracil Oxaliplatin Leucovorin Levoleucovorin Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents |
ClinicalTrials.gov processed this record on June 18, 2013