Study to Identify Mechanisms of Resistance to Standard Therapy in Patients With Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Other: Needle core biopsies of liver metastasis
- Registration Number
- NCT00984048
- Lead Sponsor
- Jewish General Hospital
- 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.
- 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庐). An alternative regimen of cytotoxic drugs, also used with Avastin庐, 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 160
- 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).
- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description FOLFOX, XELOX or FOLFIRI +/- bevacizumab Needle core biopsies of liver metastasis 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.
- Primary Outcome Measures
Name Time Method Changes in biomarkers in patients that have acquired clinical resistance. 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
Name Time Method Number of participants with adverse events relating to the liver biopsy procedure 3 years
Trial Locations
- Locations (15)
H么pital Notre-Dame
馃嚚馃嚘Montreal, Quebec, Canada
Jewish General Hospital
馃嚚馃嚘Montreal, Quebec, Canada
McGill University Health Centre
馃嚚馃嚘Montreal, Quebec, Canada
H么tel-Dieu du Qu茅bec
馃嚚馃嚘Qu茅bec, Quebec, Canada
Mount Sinai Hospital
馃嚚馃嚘Toronto, Ontario, Canada
H么pital Charles Lemoyne
馃嚚馃嚘Greenfield Park, Quebec, Canada
H么pital Sacr茅-Coeur
馃嚚馃嚘Montreal, Quebec, Canada
The Moncton Hospital
馃嚚馃嚘Moncton, New Brunswick, Canada
Sunnybrook Health Sciences Centre
馃嚚馃嚘Toronto, Ontario, Canada
H么pital Maisonneuve-Rosemont
馃嚚馃嚘Montreal, Quebec, Canada
Dr. Georges L. Dumont University Hospital
馃嚚馃嚘Moncton, New Brunswick, Canada
University Hospital Leuven
馃嚙馃嚜Leuven, Belgium
St-Mary's Hospital
馃嚚馃嚘Montreal, Quebec, Canada
H么pital Saint-Luc
馃嚚馃嚘Montreal, Quebec, Canada
Royal Victoria Hospital
馃嚚馃嚘Montreal, Quebec, Canada