A Study of Avapritinib vs Regorafenib in patients with Gastrointestinal and Solid Tumors.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 460

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 have 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 2 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. Patient, or legal guardian if permitted by local regulatory authorities, who provides informed consent to participate in the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 370
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

1. Patients who have received prior treatment with avapritinib or regorafenib.
2. Patients who have previously 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 2 different TKIs are used in combination, both TKIs are counted.
3. Patients who are known to be both KIT and PDGRFa wild type.
4. Patients who received any systemic anticancer therapy within 2 weeks before
randomization. Prior radiotherapy (including stereotactic radiotherapy) to major
organs within 2 weeks of randomization, 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 randomization, or venous thrombotic events such as pulmonary embolism or deep vein thrombosis within 14 days before randomization. Patients with venous thrombotic events such as pulmonary embolism or deep vein thrombosis = 14 days before randomization are not excluded provided they are on stable doses of anticoagulation, or have completed the planned anti-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 randomization.
8. Patients who have a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within one year prior to randomization.
9. Patients who have a non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.
10. Patients who have poor organ function as defined by one or more of the following laboratory parameters:
o Persistent proteinuria of NCI-CTCAE version 5.0 Grade 3 or higher
o Alanine aminotransferase and AST > 3 × ULN no hepatic metastases are present; > 5 × ULN if hepatic metastases are present.
o Total bilirubin >1.5 × ULN; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN.
o Estimated or measured creatinine clearance < 40 mL/min
o Platelet count < 90 × 109/L and ANC < 1.0 × 109/L.
o Hemoglobin < 9 g/dL. Transfusion and erythropoietin may be used to reach at least 9 g/dL, but must have been administered at least 2 weeks before randomization.
11. Patients who have received neutrophil growth factor support within 14 days of randomization.
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 randomization. Patient has significant traumatic injury within 28 days before randomization.
14. Patients who have a history of another primary malignancy that has been diagnosed or required therapy within 3 years before randomization.
15. Patients who have a history of a seizure disorder requiring anti-seizure medication.
16. Patients who have metastases to the brain.
17. Patients who are unwilling or unable to comply with scheduled visits, drug adm

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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