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Report for Clinical Trial NCT01949194

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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 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.

NCT01949194 Metastatic Colorectal Cancer
MeSH:Colorectal Neoplasms
HPO:Neoplasm of the large intestine

1 Interventions

Name: Regorafenib

Description: 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.
Type: Drug
Group Labels: 1


Primary Outcomes

Description: 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.

Measure: A biomarker (in blood or tissue) that may be predictive of level of response to regorafenib

Time: 4 years

Secondary Outcomes

Description: 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

Measure: Number of participants with adverse events

Time: Up to 3 years

Description: 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.

Measure: Progression free survival (PFS) time

Time: Time from registration to progressive disease (up to 3 years)

Description: 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.

Measure: Objective Response Rate (RR)

Time: Up to 3 years

Purpose: Treatment

Allocation: N/A

Single Group Assignment

There is one SNP


1 V600E

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. --- V600E ---

HPO Nodes