Study of Regorafenib as a 3rd-line or Beyond Treatment for Gastrointestinal Stromal Tumors (GIST)

Summary

A randomized, double-blind, placebo-controlled phase III study of regorafenib plus best supportive care versus placebo plus best supportive care for subjects with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) whose disease has progressed despite prior treatment with at least imatinib and sunitinib. The study is composed of 3 periods: A Screening Period, a Treatment Period, and a Survival Follow up Period. Subjects randomized to be treated with regorafenib will receive 160 mg po od for 3 weeks of every 4 week (28 day) cycle (ie, 3 weeks on/1 week off). In addition subjects will receive best supportive care which excludes any disease specific anti cancer therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgery. Tumor assessment will be every 4 weeks for the first 3 months, every 6 weeks for the next 3 months (through month 6), and every 8 weeks until the end of treatment, or more frequently if clinically indicated. Tumor assessments include CT or MRI and will be performed until tumor progression is seen in a central radiology review. Subjects receiving placebo who experience disease progression may be offered active treatment. Subjects who experience progression during regorafenib treatment may continue open label treatment. All subjects will enter the Survival Follow-up Period upon discontinuation of randomized study treatment.

Timeline

Start

2011-01-04

Primary completion

2012-01-26

Completion

2019-04-15

Publications

• Results Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schoffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG; GRID study investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):295-302. doi: 10.1016/S0140-6736(12)61857-1. Epub 2012 Nov 22.
• Results Poole CD, Connolly MP, Chang J, Currie CJ. Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo. Gastric Cancer. 2015 Jul;18(3):627-34. doi: 10.1007/s10120-014-0391-x. Epub 2014 Jun 24.
• Results Komatsu Y, Doi T, Sawaki A, Kanda T, Yamada Y, Kuss I, Demetri GD, Nishida T. Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial. Int J Clin Oncol. 2015 Oct;20(5):905-12. doi: 10.1007/s10147-015-0790-y. Epub 2015 Feb 6.
• Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, Unger C, Kratzschmar J, Heinig R, Boix O, Christensen O. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 2012 May 1;18(9):2658-67. doi: 10.1158/1078-0432.CCR-11-1900. Epub 2012 Mar 15.

Drugs

Indications