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 January 2014 by Jewish General Hospital
Sponsor:
Collaborators:
Quebec Clinical Research Organization in Cancer
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: January 28, 2014
Last verified: January 2014
  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: 140
Study Start Date: August 2009
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
FOLFOX + 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/bevacizumab or FOLFIRI/bevacizumab will be administered as per the standard of care at each treating institution. 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.

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
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: Suzan McNamara, PhD 514-340-8222 ext 6055 smcnamara@qcroc.ca

Locations
Canada, British Columbia
British Columbia Cancer Agency (BCCA) Not yet recruiting
Vancouver, British Columbia, Canada, V5Z 1H5
Contact: Karen Stearman    604-877-6000 ext 2320    kstearma@bccancer.bc.ca   
Principal Investigator: Gill Sharlene, MD         
Canada, New Brunswick
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
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Janet Smith    416-586-8440    JanetSmith@mtsinai.on.ca   
Principal Investigator: Ronald Burkes, MD         
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Brittany Buck    (416) 480-5000 ext 6192    brittany.buck@sunnybrook.ca   
Contact: Adam Lam    (416) 480-5000 ext 7868    <Adam.Lam@sunnybrook.ca>   
Principal Investigator: Yoo-Joung Ko, MD         
Canada, Quebec
Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Rosa Christodoulopoulos, PhD    514-340-8222 ext 3651    rchristodoulopoulos@jgh.mcgill.ca   
Contact: Caroline Rousseau, PhD    514-340-8222 ext 5074    crousseau@jgh.mcgill.ca   
Principal Investigator: Gerald Batist, 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         
Montreal General Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Marie-Claude Jonkas    514-934-1934 ext 42803    marie-claude_jonkas@muhc.mcgill.ca   
Principal Investigator: Thierry Alcindor, MD         
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         
St-Mary's Hospital Recruiting
Montreal, Quebec, Canada
Contact: Melania Cartillone, CRA    514-345-3511 ext 3981      
Principal Investigator: Richard Dalfen, 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         
Hôtel-Dieu du Québec Recruiting
Québec, Quebec, Canada, G1R 2J6
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
Fonds de la Recherche en Santé du Québec
Investigators
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
ClinicalTrials.gov Identifier: NCT00984048     History of Changes
Other Study ID Numbers: Q-CROC-01
Study First Received: September 23, 2009
Last Updated: January 28, 2014
Health Authority: Canada: Health Canada

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
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases

ClinicalTrials.gov processed this record on October 23, 2014