Study to Determine the Efficacy of Regorafenib in Metastatic Colorectal Cancer Patients and to Discover Biomarkers
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01949194|
Recruitment Status : Recruiting
First Posted : September 24, 2013
Last Update Posted : August 21, 2017
In recent years, anti-angiogenic agents have been incorporated into clinical practice for the treatment of metastatic CRC, leading to improvements in progression-free survival and overall survival. Regorafenib is an oral multi-kinase inhibitor that targets angiogenic and oncogenic kinases. Although structurally similar to another multi-kinase inhibitor, sorafenib, it appears to be pharmacologically more potent and possesses broader antiangiogenic properties.
Both sorafenib and regorafenib target BRAF wild-type and BRAF V600E mutant but the inhibition of p38 MAP kinase is a peculiar characteristic of regorafenib. A Phase I study of regorafenib as a single agent in patients with heavily pretreated CRC showed promising clinical activity with a disease control rate (PR + SD) of 59% in evaluable patients. In the Phase III trial (CORRECT), which was a randomized double-blind, placebo-controlled study comparing either regorafenib plus best supportive care (BSC) or placebo plus BSC, it was shown that regorafenib significantly increased overall survival (OS), progression-free survival (PFS) and disease control rate (DCR), independently of KRAS status. A major interest, given the data presented in the CORRECT trial, is to determine predictive biomarkers to indicate patients likely to benefit, or to be resistant to this anti-angiogenic compound.
This study aims to determine the efficacy of regorafenib as single-agent treatment for the treatment of second-line metastatic colorectal cancer and to identify predictive biomarkers in the actual metastatic tumors to be treated. In the case of metastatic CRC patients, liver lesions are frequently the most common site of metastatic deposit and these lesions can be biopsied to assess putative biomarkers. Patients will be asked to undergo a biopsy of a metastatic lesion prior to treatment, and an optional liver biopsy at the time of relapse. Using several high-throughput discovery platforms, biomarkers will be identified in the metastatic tumor specimens and in blood samples collected throughout the treatment. This will allow us to evaluate putative biomarkers and monitor tumor biomarker dynamics using serial blood collection.
The objectives of this trial are to help identify the patient subgroup most likely to be responsive or resistant to regorafenib, so that future treatment with regorafenib can be directed to the more responsive but as yet identified patient population.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer||Drug: Regorafenib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||52 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 Regorafenib in Patients With Metastatic Colorectal Cancer Who Have Failed First-line Therapy|
|Actual Study Start Date :||September 2013|
|Estimated Primary Completion Date :||February 2018|
|Estimated Study Completion Date :||February 2018|
The dose of regorafenib given will be 160 mg once a day (od) oral (po), using a 21 days on / 7 days off treatment schedule. This equates to four (4) tablets once a day for three (3) weeks. The patient should take the dose at the same time each day, with a full glass of water, and following a light meal. A "light meal"consists of less than 30% fat and around 300-550 calories.
Other Name: BAY 73-4506
- A biomarker (in blood or tissue) that may be predictive of level of response to regorafenib [ Time Frame: 4 years ]A biopsy from a liver metastasis will be taken at baseline for discovery of biomarkers that correlate with response to regorafenib. Genomic material (DNA and RNA) will be isolated from all biopsies. Those that pass quality control (high quality DNA, RNA and >60% tumor content) will be considered evaluable. 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 regorafenib.
- Number of participants with adverse events [ Time Frame: Up to 3 years ]Assessment of safety profile of regorafenib in treated patients : report of Adverse Events according to the The NCI's Common Toxicity Criteria version 4.0
- Progression free survival (PFS) time [ 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.
- Objective Response Rate (RR) [ Time Frame: Up to 3 years ]Determination of the objective response rate (ORR: CR (complete response) +PR (partial response) +SD (stable disease)) of treated patients according to RECIST 1.1 criteria.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01949194
|Contact: Gerald Batist, MD||514 340-8222 ext firstname.lastname@example.org|
|Contact: Petr Kavan, MD, PhD||514 340-8222 ext email@example.com|
|Canada, New Brunswick|
|The Moncton Hospital (Horizon Health Network)||Recruiting|
|Moncton, New Brunswick, Canada, E1C 6Z8|
|Contact: Mrudula Avileli 506 857-5669 Mrudula.Avileli@horizonnb.ca|
|Principal Investigator: Mahmoud Abdelsalam, MD|
|Lévis, Quebec, Canada, G6V3Z1|
|Contact: Pierre Bédard, BSN 418 835-7121 ext 3048 firstname.lastname@example.org|
|Principal Investigator: Félix Couture, MD|
|Jewish General Hospital||Recruiting|
|Montreal, Quebec, Canada, H3T 1E2|
|Contact: Claudia Schanz 514 340-8222 ext 23651 email@example.com|
|Principal Investigator: Gerald Batist, MD|
|Principal Investigator: Petr Kavan, MD, PhD|
|St-Mary's Hospital Centre||Recruiting|
|Montreal, Quebec, Canada, H3T 1M5|
|Contact: Rajesh Sharma 514 345-3511 ext 3981 firstname.lastname@example.org|
|Principal Investigator: Adrian Langleben, MD|
|McGill University Health Centre||Recruiting|
|Montréal, Quebec, Canada, H4A 3J1|
|Contact: Dianna Leroux 514-934-1934 ext 35161 email@example.com|
|Principal Investigator: Thierry Alcindor, MD|
|Hopital Maisonneuve-Rosemont||Active, not recruiting|
|Montreal, Canada, H1T 2M4|
|Principal Investigator:||Gerald Batist, MD||Jewish General Hospital|
|Principal Investigator:||Petr Kavan, MD, PhD||McGill University Health Center|