Study to Identify Biomarkers of Clinical Response to Aflibercept in Patients With Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT02045030|
Recruitment Status : Terminated (Drug (Aflibercept) no longuer available for the study)
First Posted : January 24, 2014
Last Update Posted : November 16, 2016
This is a Phase II multi-center exploratory study to identify biomarkers predictive of clinical response to aflibercept in patients with metastatic colorectal cancer who have failed first-line therapy, consisting of an oxaliplatin-containing regimen in combination with bevacizumab. Patients will consent to a needle core biopsy of a liver metastatic lesion prior to starting treatment and blood samples will be collected from study patients during treatment.
An exploratory pharmacoeconomic analysis will be performed to evaluate productivity loss, quality of life and resource utilization while on treatment with aflibercept.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer||Drug: aflibercept + FOLFIRI||Phase 2|
This is a Phase II multi-center exploratory study to identify biomarkers predictive of clinical response to aflibercept in patients with metastatic colorectal cancer who have failed first-line therapy, consisting of an oxaliplatin-containing regimen in combination with bevacizumab. Patients will consent to a needle core biopsy of a liver metastatic lesion prior to starting treatment. This study will be open primarily at sites conducting the Q-CROC-01 study (NCT00984048), in which colorectal cancer patients receiving standard first-line treatment undergo a biopsy of a liver metastatic lesion before treatment and at resistance. The post-first-line treatment biopsy will be used as the pre-treatment biopsy for this trial. For patients not participating in the Q-CROC-01 study, patients will be required to undergo a liver needle core biopsy of a metastatic lesion before study treatment.
Biopsies and blood samples will be collected from all study patients. An exploratory pharmacoeconomic analysis will be performed to evaluate productivity loss, quality of life and resource utilization while on treatment with aflibercept.
A total of 52 patients will be enrolled, primarily at centers participating in the Q-CROC-01 study. The trial will close enrolment when 42 evaluable pre-treatment tumor biopsy samples have been obtained. Accrual of the total patient population is estimated to take 24-36 months with the estimated start date being February 2014.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Aflibercept in Patients With Metastatic Colorectal Cancer Who Have Failed First-Line Therapy|
|Study Start Date :||January 2014|
|Actual Primary Completion Date :||November 2016|
|Actual Study Completion Date :||November 2016|
Experimental: aflibercept and FOLFIRI
aflibercept and FOLFIRI
Drug: aflibercept + FOLFIRI
Aflibercept (Sanofi and Regeneron) targets the Vascular endothelial growth factor (VEGF) pathway that is a composite decoy receptor based on VEGFR-1 and VEGFR-2 fused to an Fc segment of IgG1. In pre-clinical assessments, aflibercept results in stronger angiogenesis inhibition than bevacizumab, exhibiting at least 100-1000 times higher affinity to the circulating VEGFs. It is postulated that in vivo, the binding of these ligands to aflibercept results in the blockade of tumor angiogenesis along with pruning of existing tumor vascular elements and reduction of VEGF-driven vascular permeability. The expected outcome is reduced growth of primary and metastatic tumors by impeding the density of tumor vasculature and diminishing the abnormal leakiness of tumor vessels that supply matrix components to the cancer.
- A biomarker (in blood or tissue) that may be predictive of level of response to aflibercept [ Time Frame: 3 years ]A biopsy from a liver metastasis will be taken at baseline for discovery of biomarkers that correlate with response to aflibercept. Genomic material (DNA and RNA) will be isolated from all biopsies. Batched analysis will be performed at the end of the study with the evaluable samples for multiplex biomarker discovery. Patient's biomarker status at baseline will be correlated with treatment effect on PFS and response (including response rate and disease control rate) to explore which biological targets may be particularly important in defining the appropriate treatment population for aflibercept.
- Progression free survival (PFS) [ Time Frame: Time from registration to progressive disease (up to 3 years) ]The time from the date of registration until the date of radiological disease progression assessed by RECIST 1.1 or until death due to any cause, even in the absence of radiological progression.
- Response rate [ Time Frame: 3 years ]Defined as complete response (CR) and partial response (PR)
- Disease control rate [ Time Frame: 3 years ]Defined as complete response (CR) + partial response (PR) + stable disease (SD).
- Number of participants with adverse events [ Time Frame: 3 years ]Assessment of safety profile of aflibercept in combination with FOLFIRI: report of Adverse Events according to the NCI's Common Toxicity Criteria version 4.0
- The quality of life impact of treating with FOLFIRI in combination with Aflibercept [ Time Frame: From date of registration until progression of disease assessed up to 36 months ]Quality of life will be evaluated by questionnaires completed by the patient.
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): NCT02045030
|CSSS Champlain-Charles-Le Moyne|
|Greenfield Park, Quebec, Canada, J4V 2H1|
|Montreal, Quebec, Canada, H1T 2M4|
|Jewish General Hospital|
|Montreal, Quebec, Canada, H3T 1E2|
|Hôpital du Sacré-Coeur de Montréal|
|Montréal, Quebec, Canada, H4J 1C5|
|Principal Investigator:||Benoit Samson, MD||CSSS Champlain-Charles-Le Moyne|