Study to Identify Mechanisms of Resistance to Standard Therapy in Patients With Metastatic Colorectal Cancer
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| ClinicalTrials.gov Identifier: NCT00984048 |
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Recruitment Status :
Active, not recruiting
First Posted : September 24, 2009
Last Update Posted : May 17, 2018
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| Condition or disease | Intervention/treatment |
|---|---|
| Colorectal Cancer | Other: Needle core biopsies of liver metastasis |
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 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 |
| Group/Cohort | Intervention/treatment |
|---|---|
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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.
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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. |
- 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
- Number of participants with adverse events relating to the liver biopsy procedure [ Time Frame: 3 years ]
Biospecimen Retention: Samples With DNA
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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 |
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.
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
| 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 | |
| Study Director: | Gerald Batist, MD | Jewish General Hospital, Segal Cancer Center |
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 |
| 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:
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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 Bevacizumab Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents |