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

UNC Lineberger Comprehensive Cancer Center

Status and phase: Completed; Phase 1

Conditions: Neutropenia; Diarrhea; Colorectal Cancer

Treatments: Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01164215

CDR0000681338 (Other Identifier)

LCCC 0918

P30CA016086 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 76 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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76 participants in 1 patient group

mFOLFOX6

Experimental group

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)

Treatment:

Drug: fluorouracil

Drug: leucovorin

Drug: oxaliplatin