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Poster display session

2239 - A randomized phase 2 study comparing different dosing approaches of induction treatment (first cycle) of regorafenib in metastatic colorectal cancer (mCRC) patients

Date

09 Sep 2017

Session

Poster display session

Presenters

Guillem Argilés Martinez

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

G. Argilés Martinez1, E. Sanz-Garcia2, M. Valladares-Ayerbes3, J.M. Viéitez4, P. Garcia-Alfonso5, C. Gravalos6, M. Tobeña7, G. Duran Ogaya8, M.T. Cano Osuna9, B. García-Paredes10, C. Santos11, M. Rodríguez-Garrote12, F. Rivera Herrero13, M.J. Safont14, A. Falcone15, F. Ciardiello16, R. Goldberg17, J. Bennouna18, J. Tabernero19, E. Aranda Aguilar9

Author affiliations

  • 1 Medical Oncology, Vall d’Hebrón Institut d’Oncologia (VHIO),, 08035 - Barcelona/ES
  • 2 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 3 Medical Oncology, Hospital Virgen del Rocío, Sevilla/ES
  • 4 Medical Oncology, Hospital Universitario Central de Asturias, 33011 - Oviedo/ES
  • 5 Medical Oncology, Hospital Universitario Gregorio Marañón, Madrid/ES
  • 6 Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 7 Medical Oncology, Hospital Santa Creu i Sant Pau, Barcelona/ES
  • 8 Medical Oncology, Hospital Universitario Regional y Virgen de la Victoria, 29010 - Malaga/ES
  • 9 Medical Oncology, University Hospital Reina Sofia. CIBERONC Instituto de Salud Carlos III, 14004 - Cordoba/ES
  • 10 Medical Oncology, Hospital Universitario Clínico San Carlos. CIBERONC Instituto de Salud Carlos III, Madrid/ES
  • 11 Medical Oncology, ICO. H. Duran i Reynals, Barcelona/ES
  • 12 Medical Oncology, Hospital Ramón y Cajal, Madrid/ES
  • 13 Medical Oncology, Hospital Universitario Marques de Valdecilla, 39008 - Santander/ES
  • 14 Medical Oncology, Hospital General de Valencia, Valencia/ES
  • 15 Oncology  , University of Pisa, 56100   - Pisa/IT
  • 16 Oncologia Medica, Dipartimento Di Internistica Clinica E Sperimentale “f. Magrassi”,, Università degli Studi della Campania Luigi Vanvitelli, 80131 - Napoli/IT
  • 17 Medical Oncology, The Ohio State James Comprehensive Cancer Center and Solove Research Institute, Columbus/US
  • 18 Medical Oncology, CHU de Nantes, 44093 - Nantes/FR
  • 19 Medical Oncology, Vall d’Hebrón Institut d’Oncologia (VHIO), 08035 - Barcelona/ES
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Resources

Abstract 2239

Background

Regorafenib is a multikinase inhibitor with broad anti-angiogenic, anti-stroma and anti-proliferative effects that improved overall survival in patients with mCRC after failure of all approved drugs in the CORRECT phase 3 trial. The different tolerability profile of regorafenib compared with other agents normally used for the treatment of colorectal cancer, caused frequent dose-reductions and interruptions, thereby jeopardizing dose-intensity and limiting incorporation of the drug as standard of care. The CORRECT trial showed that the highest rate and intensity of treatment-related adverse events occurs during the first two cycles. The standard approved dose of regorafenib (160 mg daily three weeks on/one week off) was determined in a phase 1 study and this dose was moved directly into the phase 3 trial. The immediate sub-MTD dose level of 120mg daily 3 weeks on/1 week off did not show any DLT among 7 patients treated in the phase I. In addition, an intermittent dose approach consisting of regorafenib 160 mg daily on a 1 week on/1 week off schedule was tested in combination with chemotherapy in the CORDIAL trial and showed a favorable safety profile.

Trial design

This randomized phase 2 study will evaluate the tolerability regorafenib using different dose-escalation approaches in patients with treatment refractory mCRC. Patients will be randomized 1:1:1 to receive regorafenib at the standard approved dose (arm A), or at 120 mg daily 3 weeks on/one week off during the first cycle (arm B), or 160 mg daily one week on/one week off during the first cycle (arm C). In arms B and C, the dose will be escalated to the standard dose from cycle two onwards if no limiting toxicity appears. The primary objective is to compare the safety profile of the different treatment arms. Secondary aims include assessment of the percentage of total administered dose over the planned dose, dose intensity during the treatment period and during first two cycles, disease control rate, progression-free survival, time to treatment failure, and overall survival. The trial is in progress; 160 of 295 planned patients have been recruited at the end of March 2017 (first patient 15 July 2016).

Clinical trial identification

NCT02835924

Legal entity responsible for the study

Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) in collaboration with UNICANCER GI

Funding

Bayer HealthCare Pharmaceuticals Inc Company

Disclosure

J.M. Viéitez: Consultant or advisory relationship: Amgen, Roche. Honoraria: Servier, Shire. Research funding: Amgen, Roche, Merck Serono. A. Falcone: Consultant or advisory relationship, research funding and honoraria: Amgen, Bayer, Roche, Merck, Servier, Sanofi. F. Ciardiello: Advisory Boards (compensate): Bayer, Roche, Merck, Amgen, Lilly. Research funds: Bayer, Roche. J. Bennouna: Consultant or advisory relationship and honoraria: Roche, BMS, Boehringer-Ingelheim, Astra-Zeneca. J. Tabernero: Consultant or advisory relationship and honoraria: Roche, BMS, Boehringer-Ingelheim, Astra-Zeneca. E. Aranda Aguilar: Advisory role: Amgen, Bayer, Celgene, Merk, Roche, Sanofi. All other authors have declared no conflicts of interest.

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