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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 March 2016 by Jewish General Hospital
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00984048
First received: September 23, 2009
Last updated: March 30, 2016
Last verified: March 2016
  Purpose
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
Criteria

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 ClinicalTrials.gov identifier: NCT00984048

Contacts
Contact: Mathilde Couetoux du Tertre, PhD 514-282-4523 ext 207 mcouetoux@qcroc.ca

Locations
Belgium
University Hospital Leuven Recruiting
Leuven, Belgium
Contact: Bieke Wilmsen    +32 16 340751    bieke.wilmsen@uzleuven.be   
Principal Investigator: Hans Prenen         
Canada, British Columbia
British Columbia Cancer Agency (BCCA) Withdrawn
Vancouver, British Columbia, Canada, V5Z 1H5
Canada, New Brunswick
The Moncton Hospital Recruiting
Moncton, New Brunswick, Canada, E1C 6Z8
Contact: Mrudula Avileli    (506) 857- 5669    Mrudula.Avileli@horizonnb.ca   
Principal Investigator: Mohammed Harb, MD         
Dr. Georges L. Dumont University Hospital Recruiting
Moncton, New Brunswick, Canada, E1C 8X3
Contact: Marie-Eve Gingras    (506) 862-3779    marie-eveg@canceratl.ca   
Principal Investigator: Eve St-Hilaire, MD         
Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Suganthi Suren    (416) 480-5000 ext 82192    suganthi.suren@sunnybrook.ca   
Principal Investigator: Yoo-Joung Ko, MD         
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Janet Smith    416-586-8440    JanetSmith@mtsinai.on.ca   
Principal Investigator: Ronald Burkes, MD         
Canada, Quebec
Hôpital Charles Lemoyne Recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
Contact: Amélie Valcourt    450-466-5000 ext 3373    amelie.valcourt@rrsss16.gouv.qc.ca   
Principal Investigator: Benoit Samson, MD         
Hôpital Maisonneuve-Rosemont Recruiting
Montreal, Quebec, Canada, H1T 2M4
Contact: Darly Cham    514-252-3400 ext 4670    dcham.hmr@ssss.gouv.qc.ca   
Principal Investigator: Lucas Sideris, MD         
Hôpital Notre-Dame Recruiting
Montreal, Quebec, Canada, H2L 4M1
Contact: Annie Lebrasseur    514 890-8000 ext 24831    annie.lebrasseur.chum@ssss.gouv.qc.ca   
Principal Investigator: Mustapha Tefhé, MD         
Hôpital Saint-Luc Active, not recruiting
Montreal, Quebec, Canada, H2X 3J4
Royal Victoria Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Ayat Salman    514-934-1934 ext 31917    ayat.salman@muhc.mcgill.ca   
Principal Investigator: Peter Metrakos, MD         
Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Rosa Christodoulopoulos, PhD    514-340-8222 ext 3651    rchristodoulopoulos@jgh.mcgill.ca   
Principal Investigator: Gerald Batist, MD         
McGill University Health Centre Recruiting
Montreal, Quebec, Canada, H4A 3J1
Contact: Marie-Claude Joncas    514-934-1934 ext 48186    marie-claude.joncas@muhc.mcgill.ca   
Contact: Linda Chin    514-934-1934 ext 42560    linda.chin@muhc.mcgill.ca   
Principal Investigator: Thierry Alcindor, MD         
Hôpital Sacré-Coeur Recruiting
Montreal, Quebec, Canada
Contact: Caroline Chagnon    514-338-2222 ext 2816    caroline.chagnon@crhsc.rtss.qc.ca   
Principal Investigator: Bernard Lespérance, MD         
St-Mary's Hospital Recruiting
Montreal, Quebec, Canada
Contact: Melania Cartillone    514-345-3511 ext 3981    melania.cartillone.chsm@ssss.gouv.qc.ca   
Principal Investigator: Richard Dalfen, MD         
Hôtel-Dieu du Québec Recruiting
Québec, Quebec, Canada, G1R 2J6
Contact: Maryse Gingras    418-691-5781    maryse.gingras@chuq.qc.ca   
Contact: Theresa Jones    418-691-1581    theresa.jones@chuq.qc.ca   
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
Investigators
Study Director: Gerald Batist, MD Jewish General Hospital, Segal Cancer Center
  More Information

Additional Information:
Responsible Party: Gerald Batist, Principal Investigator, Jewish General Hospital
ClinicalTrials.gov Identifier: NCT00984048     History of Changes
Other Study ID Numbers: Q-CROC-01 
Study First Received: September 23, 2009
Last Updated: March 30, 2016
Health Authority: Canada: Health Canada
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Jewish General Hospital:
Colorectal cancer
FOLFOX
FOLFIRI
Avastin
Metastases
Liver
Colon cancer
Biomarkers
Resistance
Biobanking
Colorectal cancer with unresectable metastases to the liver

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 28, 2016