Gastrointestinal stromal tumor sarcomas of soft tissue in the gastrointestinal tract
Conditions
Interventions
Patients will be randomly assigned, in a 1:1 ratio, to 1 of 2 treatment arms:
Arm A (avapritinib) or Arm B (regorafenib) stratified by treatment regimen
(third vs. fourth), geographic region (Asia v
no maximum
treatment duration has been set. After C1, patients may continue to receive
study drug until precluded by toxicity, noncompliance, pregnancy, withdrawal of
consent, physician decision, p
Sponsors
Blueprint Medicines Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients who are * 18 years of age. 2. Patients who have GIST, which is histologically confirmed metastatic and/or unresectable (confirmed to be unresectable by a qualified surgeon). 3. Patients who received imatinib and 1 or 2 other TKIs for the treatment of GIST, including TKIs used for adjuvant therapy. Each different TKI is counted once regardless of how often it was used, and if two different TKIs are used in combination, both TKIs are counted. Patients must have disease progression prior to enrollment. Prior use of other systemic and local therapies is not restricted. 4. Patients who have an ECOG PS of 0 to 1. 5. Patients, or legal guardian if permitted by local regulatory authorities, who provides informed consent to participate in the study.
Exclusion criteria
Exclusion criteria: 1. Patients who have received prior treatment with avapritinib or regorafenib. 2. Patients who have received more than 3 different TKIs for the treatment of GIST, including TKIs used for adjuvant therapy. Each different TKI is counted once regardless of how often it was used, and if two different TKIs are used in combination, both TKIs are counted. 3. Patients who are known to be both KIT and PDGRF* wild type. 4. Patients who received any systemic anticancer therapy within 1 week before the first dose of study drug. Prior radiotherapy (including stereotactic radiotherapy) to major organs within 2 weeks of the first dose of study drug, or focal radiotherapy, (including stereotactic radiotherapy), such as to bones, limbs, or other areas not involving major organs, within 3 days. 5. Patients who have clinically significant, uncontrolled, cardiovascular disease, including congestive heart failure Grades II, III or IV according to the New York Heart Association classification, myocardial infarction or unstable angina within the previous 6 months, or uncontrolled hypertension. 6. Patients who have experienced arterial thrombotic or embolic events such as cerebrovascular accident within 6 months before the first dose of study drug, or venous thrombotic events such as pulmonary embolism within the 14 days before the first dose of study drug or deep vein thrombosis within 14 days before the first dose of study drug. Patients with venous thrombotic events such as pulmonary embolism or deep vein thrombosis * 14 days before the first dose of study drug are not excluded provided they are on stabel dosis of anticoagulation, or have completed the planned coagulation regimen. 7. Patients who have experienced any hemorrhage or bleeding event NCI CTCAE version 5.0 Grade 3 or higher within 4 weeks before the first dose of study drug. 8. Patients who have a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or history of intracranial bleeding within one year prior to randomization. 9. Patients who have a symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture. 10. Patients who have poor organ function as defined by one or more laboratory parameters, as described in the protocol. 11. Patients who have received neutrophil growth factor support within 14 days of the first dose of study drug. 12. Patients who require therapy with a concomitant medication that is a strong inhibitor or strong or moderate inducer of CYP3A4. 13. Patients who have had a major surgical procedure within 14 days of the first dose of study drug. Patient has significant traumatic injury within 28 days before the first dose of study drug. 14. Patients who have a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of study drug. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational agent may be included after approval by
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is PFS, based on central radiological assessment per mRECIST, version 1.1, in patients with advanced GIST. Progression-free survival is defined as time from randomization to disease progression, or death due to any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| The key secondary endpoints are: * Objective response rate defined as the percentage of patients whose best response is CR or PR as assessed by central radiology using mRECIST, version 1.1. * Overall survival defined as the time from date of randomization to death due to any cause. | — |
Countries
Netherlands
Outcome results
None listed