As you may be aware, there are limited treatment options available to GIST patients whose disease has progressed following treatment with imatinib and sunitinib. Bayers’s goal with this trial is to determine if it will be possible to provide regorafenib as a safe and effective treatment option for these patients.
Approximately 170 patients from 18 countries around the world will be enrolled. In the trial, patients will be randomized in a 2:1 ratio to receive either regorafenib 160 mg once daily, 3 weeks on/1 week off, or else a placebo, and it will be double blinded such that neither patients nor physicians will know who is on the drug. However, patients on placebo who have progression will be allowed to cross over to the treatment arm.
The primary endpoint of this trial is progression-free survival (PFS), and secondary endpoints include overall survival (OS), time to progression (TTP), disease control rate (DCR), tumour response rate (RR), duration of response (DOR), and safety. All patients will enter the Survival Follow-Up Period upon discontinuation of study treatment, during which assessment of survival status will be performed every three months. Patients who respond to regorafenib will be allowed to stay on treatment indefinitely.
Bayer recognises there may be concern about the placebo arm of the trial, and explains: “We implemented this design in order to establish the safety and efficacy of regorafenib in this specific patient population, for which there is no existing standard of care. While we recognize that patients who are randomized into the placebo arm may not benefit from being included in this trial at first, it is important to note that the study design includes a “cross-over” procedure, for which patients who were treated with placebo will have the option to begin treatment with regorafenib after tumour progression. Again, our ultimate goal with this Phase III trial is to establish the safety and efficacy of regorafenib in this specific patient setting. The trial was carefully designed in an effort to reach this goal.”
Some background information: Regorafenib is an investigational, potent oral multi-kinase inhibitor of angiogenic, stromal and oncogenic (receptor tyrosine) kinases (TK). Regorafenib inhibits angiogenic kinases like receptors for VEGF and the TIE2 receptor which play central roles in angiogenesis. It also inhibits various oncogenic kinases including RAF, RET and c-KIT, thereby helping to stop the proliferation of cancer cells.
Regorafenib has shown potent antitumor activity in preclinical studies by inhibiting tumour growth in multiple xenograft models via antiangiogenic and antiproliferative mechanisms. Based on these results, regorafenib is currently being investigated in clinical trials for its potential to treat patients with various tumor types. Clinical activity of regorafenib was recently shown in Phase I and II clinical studies in a variety of tumour types.
The GRID-Trial in facts & figures: