Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol

BMJ Open. 2015 Mar 9;5(3):e007189. doi: 10.1136/bmjopen-2014-007189.


Introduction: Regorafenib was recently approved for patients with pretreated advanced colorectal cancer (aCRC), despite a moderate improvement of the patients' outcome, and significant toxicities. Based on previous studies showing that early fluorodeoxyglucose-positron emission tomography (FDG-PET)-based metabolic response assessment (MRA) might adequately select patients unlikely to benefit from treatment, the RegARd-C trial uses early MRA to identify likely non-responders to regorafenib in a population of patients with aCRC and guide a comprehensive evaluation of genomic and epigenetic determinants of resistance to treatment.

Methods and analysis: RegARd-C is a multicentric prospective study. Its primary objective is to identify non-benefitters from regorafenib given at 160 mg/day, 3 weeks out of 4 in a population of patients with pretreated aCRC. Baseline PET is repeated at day 14 of the first treatment course. MRA is blinded for the investigators. Overall survival (OS) is the primary end point and will be correlated with metabolic parameters and (epi)genetic alterations assessed from tumour and serial blood samples. A target sample size of 105 evaluable patients (70 as derivation set and 35 as validation set), is considered as sufficient to validate an expected HR for OS of metabolic responders compared to metabolic non-responders significantly <1 (with 80% power and 1-sided 5% α in case of a true HR≤0.59 and a responders rate of 47%).

Ethics and dissemination: The study was approved by the Institut Jules Bordet's competent ethics committee and complies with the Helsinki declaration or the Belgian laws and regulations, whichever provides the greatest protection for the patient, and follows the International Conference on Harmonisation E 6 (R1) Guideline for Good Clinical Practice, reference number CPMP/ICH/135/95. The protocol and the trials results, even inconclusive, will be presented at international oncology congresses, and published in peer-reviewed journals. Genomic and epigenetic data will be made available in public open data sets.

Trial registration numbers: EudraCT number: 2012-005655-16; number: NCT01929616.


Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnostic imaging
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Epigenesis, Genetic
  • Fluorodeoxyglucose F18
  • Humans
  • Multimodal Imaging
  • Patient Selection
  • Phenylurea Compounds / therapeutic use*
  • Positron-Emission Tomography
  • Prospective Studies
  • Pyridines / therapeutic use*
  • Research Design*
  • Retreatment
  • Survival Rate
  • Tomography, X-Ray


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyridines
  • Fluorodeoxyglucose F18
  • regorafenib

Associated data

  • EudraCT/2012-005655-16