Study to Identify Mechanisms of Resistance to Standard Therapy in Patients With Metastatic Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Jewish General Hospital
Quebec Clinical Research Organization in Cancer
Terry Fox Research Institute
Fonds de la Recherche en Santé du Québec
Information provided by (Responsible Party):
Gerald Batist, Jewish General Hospital Identifier:
First received: September 23, 2009
Last updated: October 28, 2015
Last verified: October 2015
This is a multicenter translational study to understand therapeutic resistance in patients undergoing first-line chemotherapy (FOLFOX/Avastin, or FOLFIRI/Avastin) for metastatic colorectal cancer. Tissue samples from 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.

Condition Intervention
Colorectal Cancer
Other: Needle core biopsies of liver metastasis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to Standard First-line Therapy in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:

Further study details as provided by Jewish General Hospital:

Primary Outcome Measures:
  • Changes in biomarkers in patients that have acquired clinical resistance. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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

Secondary Outcome Measures:
  • Number of participants with adverse events relating to the liver biopsy procedure [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA
Tumor tissue from a hepatic metastasis will be removed by needle core biopsy (NCB) obtained under radiologic guidance and will be flash-frozen. To obtain sufficient material for tissue banking, three needle core biopsies (NCB) will be removed from the same metastasis. Additionally, monthly whole blood samples will be collected, as well as plasma.

Estimated Enrollment: 180
Study Start Date: August 2009
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

Detailed Description:

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
This study will be conducted in patients with a confirmed diagnosis of colorectal cancer with the presence of liver metastasis, who will be receiving first-line treatment (FOLFOX/bevacizumab or FOLFIRI/bevacizumab) for metastatic disease.

Inclusion Criteria:

  1. Patients with a histologically confirmed diagnosis of colorectal cancer, with at least one liver metastasis site available for biopsy.
  2. For patients with liver only disease, patients deemed not to be initially resectable
  3. Scheduled to receive first-line chemotherapy (FOLFOX/bevacizumab or FOLFIRI/bevacizumab) for metastatic disease.
  4. Measurable metastatic disease (at least one unidimensionally measurable lesion) present after planned biopsy of metastatic site(s).
  5. ECOG 0, 1 or 2.
  6. Life expectancy of 12 or more weeks.
  7. Age > 18 years.
  8. Able to adhere to the study visit schedule and other protocol requirements.
  9. Normal coagulation profile (PT, PTT, INR).

Exclusion Criteria:

  1. Patients with initially resectable liver only metastases
  2. Have received prior therapy for metastatic cancer. Prior adjuvant therapy is allowed.
  3. Inadequate or unusable tissue as the only tissue available for biopsy.
  4. Contraindication to any of the components of the the first-line chemotherapy regimen.
  5. Known brain metastases or meningeal disease.
  6. Female patients who are pregnant or breastfeeding.
  7. Concurrent treatment with other anti-cancer therapy (palliative radiation is allowed but patients must have a metastatic site available for re-biopsy that has not been irradiated).
  8. Abnormal coagulation profile, any anti-coagulant therapy.
  9. Known infection with HIV.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00984048

Contact: Mathilde Couetoux du Tertre, PhD 514-282-4523 ext 207

University Hospital Leuven Recruiting
Leuven, Belgium
Contact: Bieke Wilmsen    +32 16 340751   
Principal Investigator: Hans Prenen         
Canada, British Columbia
British Columbia Cancer Agency (BCCA) Withdrawn
Vancouver, British Columbia, Canada, V5Z 1H5
Canada, New Brunswick
Dr. Georges L. Dumont University Hospital Recruiting
Moncton, New Brunswick, Canada, E1C 8X3
Contact: Marie-Eve Gingras    (506) 862-3779   
Principal Investigator: Eve St-Hilaire, MD         
The Moncton Hospital Recruiting
Moncton, New Brunswick, Canada, E1C 6Z8
Contact: Mrudula Avileli    (506) 857- 5669   
Principal Investigator: Mohammed Harb, MD         
Canada, Ontario
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Janet Smith    416-586-8440   
Principal Investigator: Ronald Burkes, MD         
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Suganthi Suren    (416) 480-5000 ext 82192   
Principal Investigator: Yoo-Joung Ko, MD         
Canada, Quebec
Hôpital Charles Lemoyne Recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
Contact: Amélie Valcourt    450-466-5000 ext 3373   
Principal Investigator: Benoit Samson, MD         
St-Mary's Hospital Recruiting
Montreal, Quebec, Canada
Contact: Melania Cartillone    514-345-3511 ext 3981   
Principal Investigator: Richard Dalfen, MD         
Hôpital Maisonneuve-Rosemont Recruiting
Montreal, Quebec, Canada, H1T 2M4
Contact: Darly Cham    514-252-3400 ext 4670   
Principal Investigator: Lucas Sideris, MD         
Hôpital Notre-Dame Recruiting
Montreal, Quebec, Canada, H2L 4M1
Contact: Annie Lebrasseur    514 890-8000 ext 24831   
Principal Investigator: Mustapha Tefhé, MD         
Hôpital Sacré-Coeur Recruiting
Montreal, Quebec, Canada
Contact: Caroline Chagnon    514-338-2222 ext 2816   
Principal Investigator: Bernard Lespérance, MD         
Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Rosa Christodoulopoulos, PhD    514-340-8222 ext 3651   
Principal Investigator: Gerald Batist, MD         
Montreal General Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Marie-Claude Jonkas    514-934-1934 ext 42803   
Principal Investigator: Thierry Alcindor, MD         
Royal Victoria Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Ayat Salman    514-934-1934 ext 31917   
Principal Investigator: Peter Metrakos, MD         
Hôpital Saint-Luc Active, not recruiting
Montreal, Quebec, Canada, H2X 3J4
Hôtel-Dieu du Québec Recruiting
Québec, Quebec, Canada, G1R 2J6
Contact: Maryse Gingras    418-691-5781   
Contact: Theresa Jones    418-691-1581   
Principal Investigator: Felix Couture, MD         
Hopital Fleurimont Withdrawn
Sherbrooke, Quebec, Canada
Sponsors and Collaborators
Jewish General Hospital
Quebec Clinical Research Organization in Cancer
Terry Fox Research Institute
Fonds de la Recherche en Santé du Québec
Study Director: Gerald Batist, MD Jewish General Hospital, Segal Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Gerald Batist, Principal Investigator, Jewish General Hospital Identifier: NCT00984048     History of Changes
Other Study ID Numbers: Q-CROC-01
Study First Received: September 23, 2009
Last Updated: October 28, 2015
Health Authority: Canada: Health Canada

Keywords provided by Jewish General Hospital:
Colorectal cancer
Colon cancer
Colorectal cancer with unresectable metastases to the liver

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Rectal Diseases processed this record on December 01, 2015