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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.
Verified August 2017 by Gerald Batist, Jewish General Hospital
Sponsor:
Jewish General Hospital
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: August 16, 2017
Last verified: August 2017
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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 Gerald Batist, Jewish General Hospital:
Primary Outcome Measures:
- 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:
- 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.
| 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) |
| 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:
- Patients with a histologically confirmed diagnosis of colorectal cancer, with at least one liver metastasis site available for biopsy.
- For patients with liver only disease, patients deemed not to be initially resectable
- Scheduled to receive first-line chemotherapy (FOLFOX/bevacizumab or FOLFIRI/bevacizumab) for metastatic disease.
- Measurable metastatic disease (at least one unidimensionally measurable lesion) present after planned biopsy of metastatic site(s).
- ECOG 0, 1 or 2.
- Life expectancy of 12 or more weeks.
- Age > 18 years.
- Able to adhere to the study visit schedule and other protocol requirements.
- Normal coagulation profile (PT, PTT, INR).
Exclusion Criteria:
- Patients with initially resectable liver only metastases
- Have received prior therapy for metastatic cancer. Prior adjuvant therapy is allowed.
- Inadequate or unusable tissue as the only tissue available for biopsy.
- Contraindication to any of the components of the the first-line chemotherapy regimen.
- Known brain metastases or meningeal disease.
- Female patients who are pregnant or breastfeeding.
- 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).
- Abnormal coagulation profile, any anti-coagulant therapy.
- Known infection with HIV.
Contacts and Locations
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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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00984048
Contacts
| Contact: Mathilde Couetoux du Tertre, PhD | 514-282-4523 ext 207 | mcouetoux@exactis.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: Claudia Schanz 514-340-8222 ext 23651 cschanz@jgh.mcgill.ca | |
| Principal Investigator: Gerald Batist, MD | |
| St-Mary's Hospital | Recruiting |
| Montreal, Quebec, Canada, H3T 1M5 | |
| Contact: Rajesh Sharma 514-345-3511 ext 3981 rajesh.sharma.comtl@ssss.gouv.qc.ca | |
| Principal Investigator: Richard Dalfen, 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 | |
| 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: | August 16, 2017 |
| 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:
|
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 21, 2017