Study to Identify Mechanisms of Resistance to Standard Therapy in Patients With Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT00984048|
Recruitment Status : Unknown
Verified May 2018 by Gerald Batist, Jewish General Hospital.
Recruitment status was: Active, not recruiting
First Posted : September 24, 2009
Last Update Posted : May 17, 2018
|Condition or disease||Intervention/treatment|
|Colorectal Cancer||Other: Needle core biopsies of liver metastasis|
The major obstacle to the cure of cancer by pharmacological agents is resistance to these agents. Clinical responses of metastatic cancers to the most advanced chemotherapeutic agents usually range from 15 to 40%, indicating that intrinsic resistance, and acquired resistance occurs almost inevitably in those tumors that do respond. In patients with metastatic colorectal cancer, clinical resistance to a particular treatment is a clear endpoint (tumor growth), and is usually observed within 6-12 months of any given therapy. Thus, drug resistance and selecting appropriate therapeutic alternatives for drug-resistant cancer remain major dilemmas for oncologists.
The current first-line treatment for metastatic colorectal cancer in Quebec and much of North America is a combination called FOLFOX (the fluoro-pyrimidine 5-FU given as a 46-hour infusion, folinic acid and oxaliplatin) in combination with bevacizumab (Avastin®). An alternative regimen of cytotoxic drugs, also used with Avastin®, is FOLFIRI, which simply replaces oxaliplatin with the topoisomerase inhibitor irinotecan. In the metastatic setting, studies have not demonstrated significant differences between the two regimens, such that decision-making lacks definitive tools.
The objective of this study is to identify, in clinical samples, the molecular signature of clinically resistant colorectal cancer (CRC) patients for the most current and commonly used therapeutic agents. The goals of this study are two-fold. First, to build a biobank of blood and tissue specimens, prior to starting chemotherapy and at a determined time-point (progression of disease), from patients undergoing the same standard and well established first-line treatments (FOLFOX/bevacizumab or FOLFIRI/bevacizumab) for metastatic colorectal cancer. Second, to use state-of-the-art approaches by various collaborating laboratories to correlate clinical outcomes with molecular events that can be used to predict and circumscribe chemoresistance.
|Study Type :||Observational|
|Actual Enrollment :||160 participants|
|Official Title:||Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to Standard First-line Therapy in Patients With Metastatic Colorectal Cancer|
|Study Start Date :||August 2009|
|Actual Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||September 2018|
FOLFOX, XELOX or FOLFIRI +/- bevacizumab
Patients are scheduled to receive first-line treatment for metastatic disease. They should be receiving at least one component of either FOLFOX, XELOX or FOLFIRI regimen with or without bevacizumab.
Other: Needle core biopsies of liver metastasis
No investigational products will be administered to subjects as part of this translational research study. A first-line chemotherapy regimen consisting of FOLFOX, XELOX or FOLFIRI +/- bevacizumab will be administered as per the standard of care at each treating institution. Needle core biopsies of liver metastasis will be collected and banked before the start of chemotherapy and at the time of progression. Additionally, blood samples will be drawn monthly and stored in the tissue biobank.
- Changes in biomarkers in patients that have acquired clinical resistance. [ Time Frame: 4 years ]Liver needle core biopsies are obtained pre-treatment and at progression of disease from all patients. These are used to discover exploratory biomarkers of resistance to FOLFOX/bevacizumab and FOLFIRI/bevacizumab
- Number of participants with adverse events relating to the liver biopsy procedure [ Time Frame: 3 years ]
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00984048
|University Hospital Leuven|
|Canada, New Brunswick|
|The Moncton Hospital|
|Moncton, New Brunswick, Canada, E1C 6Z8|
|Dr. Georges L. Dumont University Hospital|
|Moncton, New Brunswick, Canada, E1C 8X3|
|Sunnybrook Health Sciences Centre|
|Toronto, Ontario, Canada, M4N 3M5|
|Mount Sinai Hospital|
|Toronto, Ontario, Canada, M5G 1X5|
|Hôpital Charles Lemoyne|
|Greenfield Park, Quebec, Canada, J4V 2H1|
|Montreal, Quebec, Canada, H1T 2M4|
|Montreal, Quebec, Canada, H2L 4M1|
|Montreal, Quebec, Canada, H2X 3J4|
|Royal Victoria Hospital|
|Montreal, Quebec, Canada, H3A 1A1|
|Jewish General Hospital|
|Montreal, Quebec, Canada, H3T 1E2|
|Montreal, Quebec, Canada, H3T 1M5|
|McGill University Health Centre|
|Montreal, Quebec, Canada, H4A 3J1|
|Montreal, Quebec, Canada|
|Hôtel-Dieu du Québec|
|Québec, Quebec, Canada, G1R 2J6|
|Study Director:||Gerald Batist, MD||Jewish General Hospital, Segal Cancer Center|