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

NCT01164215 | Completed Phase 1 DMC

• 3 other identifiers: LCCC 0918P30CA016086CDR0000681338
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  During first 4 cycles of drug therapy

Secondary Outcomes (1)

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

  24 months

Study Arms (1)

mFOLFOX6

EXPERIMENTAL

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; Drug: leucovorin; Drug: oxaliplatin

Interventions

fluorouracil DRUG

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

Also known as: 5FU

mFOLFOX6

leucovorin DRUG

200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks

Also known as: leucovorin calcium

mFOLFOX6

oxaliplatin DRUG

85 mg/m2, intravenously for 2 hours, once every 2 weeks

Also known as: Eloxatin

mFOLFOX6

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Cancer Care of Western North Carolina

Asheville, North Carolina, 28801, United States

Location

Moses Cone Regional Cancer Center at Wesley Long Community Hospital

Greensboro, North Carolina, 27403-1198, United States

Location

Leo W. Jenkins Cancer Center at ECU Medical School

Greenville, North Carolina, 27834, United States

Location

Rex Cancer Center at Rex Hospital

Raleigh, North Carolina, 27607, United States

Location

Marion L. Shepard Cancer Center

Washington, North Carolina, 27889, United States

Location

Related Publications (2)

• 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.

  PMID: 29159476 DERIVED

• 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.

  PMID: 25117066 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Diarrhea; Neutropenia; Colonic Neoplasms; Rectal Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

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; Pathological Conditions, Signs and Symptoms; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Christine M. Walko, PharmD, BCOP

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 16, 2010
• Study Start: February 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: September 1, 2013
• Last Updated: October 9, 2015

Record last verified: 2015-10

Locations

US (5)