P-306 - A phase II biopsy-driven study to identify biomarkers predictive of clinical response to second-line regorafenib in patients with metastatic colorec...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anticancer Agents
Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter A. Schab
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors A. Schab1, G. Batist2, P. Kavan3, M. Abdelsalam4, F. Aubin5, A. Langleben6, F. Couture7, A. Gologan3, A. Constantin3, E. Camlioglu3, C. Hoffert1
  • 1Quebec-Clinical Research Organization in Cancer, Montreal/CA
  • 2Department Of Oncology, McGill University and the Segal Cancer Center, Sir Mortimer B. Davis, Jewish General Hospital, Montreal/CA
  • 3Jewish General Hospital, Montreal/CA
  • 4The Moncton Hospital, Moncton/CA
  • 5CHUM - Hopital Notre-Dame, Montreal/CA
  • 6St-Mary's Hospital, Montreal/CA
  • 7CHAU Lévis, Levis/CA



A major challenge in advancing treatment for metastatic colorectal cancer (mCRC) is to identify biomarkers (BMs) predictive of response. We began a phase II investigator-initiated study to identify BMs predictive of response or resistance to regorafenib in blood and tumor tissue in patients with mCRC who failed first-line therapy (QCROC-06; NCT01949194). Regorafenib is an oral multikinase inhibitor that targets angiogenic, stromal and oncogenic kinases. The phase III CORRECT and CONCUR trials demonstrated that regorafenib monotherapy significantly increased overall survival in patients with mCRC1,2. Our objective is to determine predictive biomarkers to indicate which mCRC patients will likely benefit or be resistant to regorafenib.


Patients with mCRC who failed first-line treatment (FOLFOX or FOLFIRI +/- bevacizumab) will receive regorafenib monotherapy in second-line and undergo a pre-treatment biopsy of a metastatic lesion site. A biopsy at disease progression is optional. The primary objective is to identify BMs of response or resistance in tumor tissue and blood. Secondary objectives include progression free survival, response rate, safety and feasibility of obtaining metastatic biopsies. Patients are recruited at 5 Canadian centers to collect 42 evaluable pre-treatment biopsies. Eighteen patients have been enrolled so far. Patients are largely recruited after participating in QCROC-01, a study to identify BMs of mCRC resistance to first-line therapy. The biopsy collected at resistance to first-line treatment in Q-CROC-01 is serving as the entry biopsy for QCROC-06. Genomic material will be isolated from all biopsies, and blood is collected for analysis of VEGF polymorphism and circulating tumor DNA. BMs will be identified using targeted and global profiling approaches. The trial is supported by Bayer HealthCare.

1Grothey et al. Regorafenib monotherapy for previously treated mCRC (CORRECT): an international, multicenter, randomised, placebo-controlled, Phase 3 trial. The Lancet 381: 303-312, 2012

2Kim T et al: CONCUR: A randomized, placebo-controlled phase 3 study of regorafenib monotherapy in Asian patients with previously treated metastatic colorectal cancer. ESMO 2014 Congress Abstract 500