An open label randomised trial for adults with histologically confirmed measurable metastatic GIST who have received no other treatment for metastatic disease. The study aims to determine if an alternating regimen of imatinib and regorafenib has sufficient activity and safety in comparison to imatinib alone to warrant further evaluation as a first line treatment for metastatic GIST.
Name: Regorafenib
Type: DrugArm B
Name: imatinib
Type: DrugArm A Arm B
Description: PFS at 24 months as calculated from the time from either (i) randomization if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib) to the date of progression as determined by RECIST v1.1
Measure: Progression free survival at 24 months (disease progression or death) Time: 24 MonthsDescription: Objective tumour response rate following 2 cycles of treatment
Measure: Objective tumour response rate at 16 weeks Time: 16 weeksDescription: Clinical benefit rate (SD + PR + CR) following 2 cycles of treatment
Measure: Clinical benefit rate at 16 weeks Time: 16 weeksDescription: complete response rate will be calculated by summing the number of participants assessed as having a complete response and dividing this by the total number of participants evaluable for response (according to RECIST Version 1.1).
Measure: Complete response rate Time: 5 yearsDescription: Time to treatment failure is defined as the time from either (i) randomization (if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib) to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.
Measure: Time to treatment failure Time: 5 yearsDescription: Safety/toxicity/tolerability
Measure: Adverse Events Time: 5 yearsDescription: Overall survival is defined as the interval from either (i) randomization (if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib) to date of death from any cause, or the date of last known follow-up alive.
Measure: Overall survival Time: 5 yearsDescription: This is defined as the rate of patients who proceed to surgery with the aim of resecting all remaining macroscopic disease.
Measure: Macroscopically complete removal of all residual disease by surgery Time: 5 yearsDescription: to explore the relationship between change in PET imaging during washout period of regorafenib and imatinib (in subset of participants at selected centres)
Measure: Change in PET imaging during washout period of regorafenib and imatinib in those taking part in the PET substudy Time: 3 yearsDescription: To explore the relationship between study endpoints and Imatinib plasma levels at 4 and 12 weeks after commencement of treatment in both arms. Arm B: Imatinib plasma levels at 3 and 11 weeks after commencement of treatment and regorafenib plasma levels 7 and 15 weeks after commencement of treatment.
Measure: Imatinib plasma levels 4 and 12 weeks after commencement of treatment in both arms. Arm B: Imatinib plasma levels at 3 and 11 weeks after commencement of treatment and regorafenib plasma levels 7 and 15 weeks after commencement of treatment. Time: 3 yearsDescription: To explore the relationship between study endpoints and circulating other biomarkers as prognostic and/or predictive markers.
Measure: Change in circulating serum/plasma growth factor and cytokine levels over time(multiplex assay), Frequency of KIT/PDGFRA mutations in circulating blood DNA and DNA load as prognostic and/or predictive markers Time: 3 yearsDescription: Rate of patients having macroscopically complete removal of all residual disease by surgery
Measure: Macroscopically complete removal of all residual disease by surgery Time: 3 yearsAllocation: Randomized
Parallel Assignment
There is one SNP
- The presence of PDGFR D842V mutation or other mutation known to cause imatinib resistance. --- D842V ---