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
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
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
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 tumours 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 tumour specimens and in blood samples collected throughout the treatment. This
will allow us to evaluate putative biomarkers and monitor tumour 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.
View this trial on ClinicalTrials.gov
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