title: Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol.
abstract: BACKGROUND
  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
  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%).
  
  
  BACKGROUND
  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.
  
  
  BACKGROUND
  EudraCT number: 2012-005655-16; ClinicalTrials.gov number: NCT01929616.
authors.affiliation: Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Hendlisz
authors.affiliation: Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Amélie
authors.initials: A
authors.lastname: Deleporte
authors.affiliation: Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vandeputte
authors.affiliation: Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Charette
authors.affiliation: Data Centre, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.affiliation: Nuclear Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guiot
authors.affiliation: Nuclear Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Camilo
authors.initials: C
authors.lastname: Garcia
authors.affiliation: Nuclear Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Flamen
mesh_terms: D006801:Humans; D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D044127:Epigenesis, Genetic; D019788:Fluorodeoxyglucose F18; D064847:Multimodal Imaging; D018579:Patient Selection; D010671:Phenylurea Compounds / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use; D012107:Research Design; D019233:Retreatment; D015996:Survival Rate; D014056:Tomography, X-Ray; D015337:Multicenter Studies as Topic
chemical_list: D000970:Antineoplastic Agents; D019788:Fluorodeoxyglucose F18; D010671:Phenylurea Compounds; D011725:Pyridines; C559147:regorafenib
keywords: CHEMOTHERAPY; NUCLEAR MEDICINE