SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02365441

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Randomised Phase II Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST)

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.

NCT02365441 Gastrointestinal Stromal Tumour
MeSH: Gastrointestinal Stromal Tumors
HPO: Gastrointestinal stroma tumor

2 Interventions

Name: Regorafenib

Type: Drug

Arm B

Name: imatinib

Type: Drug

Arm A Arm B


Primary Outcomes

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 Months

Secondary Outcomes

Description: Objective tumour response rate following 2 cycles of treatment

Measure: Objective tumour response rate at 16 weeks

Time: 16 weeks

Description: Clinical benefit rate (SD + PR + CR) following 2 cycles of treatment

Measure: Clinical benefit rate at 16 weeks

Time: 16 weeks

Description: 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 years

Description: 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 years

Description: Safety/toxicity/tolerability

Measure: Adverse Events

Time: 5 years

Description: 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 years

Other Outcomes

Description: 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 years

Description: 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 years

Description: 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 years

Description: 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 years

Measure: Tumour tissue biomarkers including, but not limited to, proteins relating to EGFR and PDGFR signalling and angiogenesis.

Time: 3 years

Description: 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 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 D842V

- The presence of PDGFR D842V mutation or other mutation known to cause imatinib resistance. --- D842V ---



HPO Nodes


HPO:
Gastrointestinal stroma tumor
Genes 17
CD19 MS4A1 TNFRSF13C CR2 PDGFRA TNFSF12 KIT TNFRSF13B PRKCD CD81 SDHA NFKB1 SDHB NFKB2 SDHC SDHD ICOS