Colorectal CancerNCT00984048
Study to Identify Mechanisms of Resistance to Standard Therapy in Patients With Metastatic Colorectal Cancer
An observational study of Colorectal Cancer, run by Jewish General Hospital at 15 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Needle core biopsies of liver metastasis
- How many people
- 160 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Aug 2009to Aug 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Show all 9Show fewer
- Age > 18 years.
- Able to adhere to the study visit schedule and other protocol requirements.
- Normal coagulation profile (PT, PTT, INR).
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
Canada14 sites
Hôpital Charles Lemoyne
Greenfield Park, Quebec, J4V 2H1
The Moncton Hospital
Moncton, New Brunswick, E1C 6Z8
Dr. Georges L. Dumont University Hospital
Moncton, New Brunswick, E1C 8X3
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4
Hôpital Notre-Dame
Montreal, Quebec, H2L 4M1
Hôpital Saint-Luc
Montreal, Quebec, H2X 3J4
Royal Victoria Hospital
Montreal, Quebec, H3A 1A1
Jewish General Hospital
Montreal, Quebec, H3T 1E2
St-Mary's Hospital
Montreal, Quebec, H3T 1M5
McGill University Health Centre
Montreal, Quebec, H4A 3J1
Hôpital Sacré-Coeur
Montreal, Quebec
Hôtel-Dieu du Québec
Québec, Quebec, G1R 2J6
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
About this study
Official title: Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to Standard First-line Therapy in Patients With Metastatic Colorectal Cancer
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.
Read the 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.
- Conditions
- Colorectal Cancer
- Being tested
- Needle core biopsies of liver metastasis
- Keywords
- Colorectal cancer, FOLFOX, FOLFIRI, Avastin, Metastases, Liver, Colon cancer, Biomarkers, Resistance, Biobanking, Colorectal cancer with unresectable metastases to the liver
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Needle core biopsies of liver metastasisOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Needle core biopsies of liver metastasis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in biomarkers in patients that have acquired clinical resistance.
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
Measured: 4 years
Secondary outcomes (1)
Number of participants with adverse events relating to the liver biopsy procedure
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2009 (estimated)
- Study startAug 2009
- Primary completionAug 2019
- Study completionAug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jewish General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Exactis Innovation, Terry Fox Research Institute, Fonds de la Recherche en Santé du Québec
- Responsible party
- Principal investigator, Gerald Batist, Jewish General Hospital
- Investigators
- Gerald Batist, MD, Study director, Jewish General Hospital, Segal Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00984048
- Sponsor's protocol ID
- Q-CROC-01
- Status last verified
- Jun 2021
- First submitted
- 23 Sep 2009
- Last updated
- 15 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study to Identify Molecular Mechanisms of Clinical Resistance to Standard First-line Therapy in Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00984048
- Acronym / sponsor ID
- Q-CROC-01
- Conditions
- Colorectal Cancer
- Keywords
- Colorectal cancer, FOLFOX, FOLFIRI, Avastin, Metastases, Liver, Colon cancer, Biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Jewish General HospitalUniversity, hospital or other
- Collaborators
- Exactis Innovation, Terry Fox Research Institute, Fonds de la Recherche en Santé du Québec
- Study start
- Aug 2009
- Primary completion
- Aug 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 24 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FOLFOX, XELOX or FOLFIRI +/- bevacizumab | – | Other: Needle core biopsies of liver metastasisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Needle core biopsies of liver metastasisNo 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. | Other | FOLFOX, XELOX or FOLFIRI +/- bevacizumab |
Primary outcome
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
1 secondary outcome
Number of participants with adverse events relating to the liver biopsy procedure
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2021.
- Individual participant dataSharing planned: Undecided
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerald Batist, MD study director
Jewish General Hospital, Segal Cancer Center
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Cancer, run by Jewish General Hospital at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Canada, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in biomarkers in patients that have acquired clinical resistance. (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2021.