Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer

Phase 4 Study to Characterize and Evaluate Markers of Chemoresistance in Patients With Metastatic Colorectal Cancer

RATIONALE: Studying samples of blood and tumor tissue in the laboratory from patients with cancer receiving chemotherapy may help doctors understand the effect of chemotherapy on biomarkers. It may also help doctors predict how patients will respond to treatment.

PURPOSE: This phase IV trial is studying biomarkers in patients undergoing chemotherapy for metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: pharmacological study; Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Other: laboratory biomarker analysis; Drug: oxaliplatin; Drug: capecitabine

Detailed Description

OBJECTIVES:

Primary

• Research the oncogenetic parameters and pharmacogenetic and pharmacokinetic predictors of therapeutic response and toxic effects.

Secondary

• Study the correlations between the pharmacogenetic and pharmacokinetic parameters.
• Study the predictive value of these parameters on disease-free and overall survival.

OUTLINE: This is a multicenter study.

Patients receive 1 of 4 chemotherapy regimens:

• Regimen 1: Fluorouracil and leucovorin calcium
• Regimen 2: Capecitabine and leucovorin calcium
• Regimen 3: Irinotecan hydrochloride
• Regimen 4: Oxaliplatin Tumor and blood samples are collected before the start of chemotherapy and are examined by pharmacogenetic analysis. Clinical and biological parameters are also studied. Blood samples are also collected during the first course of chemotherapy for pharmacokinetic studies.

After completion of study therapy, patients are followed periodically for 3 years.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Limoges, France, 87042
    • Centre Hospital Regional Universitaire de Limoges

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic colorectal cancer

  • Unresectable metastatic disease must be confirmed histologically if > 2 years since primary diagnosis
• Measurable metastatic disease > 1 cm by spiral CT scan or > 2 cm by other methods

• Scheduled to receive first-line chemotherapy for metastatic disease

  • Chemotherapy must include fluorouracil, capecitabine, irinotecan hydrochloride, or oxaliplatin
• No inadequate or unusable tissue as the only tissue available
• No known brain metastases or meningeal disease

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• No contraindication to chemotherapy
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other severe pathology that is likely to worsen during therapy
• No dementia or severely impaired mental condition
• No geographical or psychological reasons that would preclude treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior therapy for metastatic cancer
• Prior adjuvant chemotherapy allowed
• Concurrent bevacizumab or other monoclonal antibody therapy allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Oncogenetic parameters
Pharmacogenetic and pharmacokinetic predictors of therapeutic response and toxic effects

Secondary Outcome Measures

Outcome Measure
Correlations between the pharmacogenetic and pharmacokinetic parameters
Predictive value of pharmacogenetic and pharmacokinetic parameters on disease-free and overall survival

Collaborators and Investigators

• Sponsor: Centre Hospital Regional Universitaire de Limoges
• Investigators: Study Chair: Nicole Tubiana-Mathieu, MD, Centre Hospital Regional Universitaire de Limoges

Publications and helpful links

General Publications

• Deyme L, Barbolosi D, Mbatchi LC, Tubiana-Mathieu N, Ychou M, Evrard A, Gattacceca F. Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen. Cancer Chemother Pharmacol. 2021 Aug;88(2):247-258. doi: 10.1007/s00280-021-04255-9. Epub 2021 Apr 28.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 15, 2007
• First Submitted That Met QC Criteria: November 15, 2007
• First Posted (Estimate): November 16, 2007

Study Record Updates

• Last Update Posted (Estimate): May 16, 2011
• Last Update Submitted That Met QC Criteria: May 13, 2011
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Capecitabine; Oxaliplatin; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000574159; CHUL-BIO-COLON; INCA-RECF0356