Study to Determine the Efficacy of Regorafenib in Metastatic Colorectal Cancer Patients and to Discover Biomarkers

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


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 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.

Trial Description

Primary Outcome:

  • A biomarker (in blood or tissue) that may be predictive of level of response to regorafenib
Secondary Outcome:
  • Number of participants with adverse events
  • Progression free survival (PFS) time
  • Objective Response Rate (RR)

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Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society