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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Collaborators:
Exactis Innovation
Terry Fox Research Institute
Fonds de la Recherche en Santé du Québec
Information provided by (Responsible Party):
Gerald Batist, Jewish General Hospital

Study Description
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Brief Summary:
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 or disease Intervention/treatment
Colorectal Cancer Other: Needle core biopsies of liver metastasis

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.

Study Design
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Study Type : Observational
Actual Enrollment : 160 participants
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
Study Start Date : August 2009
Actual Primary Completion Date : December 2017
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Number of participants with adverse events relating to the liver biopsy procedure [ Time Frame: 3 years ]

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.

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

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


Locations
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Belgium
University Hospital Leuven
Leuven, Belgium
Canada, New Brunswick
The Moncton Hospital
Moncton, New Brunswick, Canada, E1C 6Z8
Dr. Georges L. Dumont University Hospital
Moncton, New Brunswick, Canada, E1C 8X3
Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Canada, Quebec
Hôpital Charles Lemoyne
Greenfield Park, Quebec, Canada, J4V 2H1
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
Hôpital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Hôpital Saint-Luc
Montreal, Quebec, Canada, H2X 3J4
Royal Victoria Hospital
Montreal, Quebec, Canada, H3A 1A1
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
St-Mary's Hospital
Montreal, Quebec, Canada, H3T 1M5
McGill University Health Centre
Montreal, Quebec, Canada, H4A 3J1
Hôpital Sacré-Coeur
Montreal, Quebec, Canada
Hôtel-Dieu du Québec
Québec, Quebec, Canada, G1R 2J6
Sponsors and Collaborators
Jewish General Hospital
Exactis Innovation
Terry Fox Research Institute
Fonds de la Recherche en Santé du Québec
Investigators
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Study Director: Gerald Batist, MD Jewish General Hospital, Segal Cancer Center
More Information
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Responsible Party: Gerald Batist, Principal Investigator, Jewish General Hospital
ClinicalTrials.gov Identifier: NCT00984048    
Other Study ID Numbers: Q-CROC-01
First Posted: September 24, 2009    Key Record Dates
Last Update Posted: May 17, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Gerald Batist, 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:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
 Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases