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

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 476

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 as prior treatment regimens, including adjuvant therapy, with objective disease progression, inadequate clinical benefit, or intolerance. Additionally, disease progression or intolerance to other systemic therapies including investigational agents and radiotherapy is allowed. Patients who experienced intolerance to prior therapies must have objective disease progression prior to enrollment onto BLU-285-1303 study.
4. Patients who have an ECOG PS of 0 to 2.
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. Prior treatment with avapritinib or regorafenib.
2. More than 3 different prior TKI treatment regimens. If a patient receives the same TKI more than once sequentially (eg, imatinib followed by a period without systemic therapy and retreatment with imatinib), that will be counted as a single TKI treatment regimen.
3. Patients who are known to be both KIT and PDGRFa wild type.
4. Any systemic anticancer therapy within 2 weeks before randomization. Prior radiotherapy to major organs within 2 weeks of randomization, or focal radiotherapy, such as to bones, limbs, or other areas not involving major organs, within 3 days.
5. Clinically significant, uncontrolled, cardiovascular disease, including congestive heart failure Grades II, III or IV according to the NYHA classification, myocardial infarction or unstable angina within the previous 6 months, or uncontrolled hypertension.
6. Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within the 6 months before randomization or venous thrombotic events such as deep vein thrombosis within the 3 months before randomization.
7. Hemorrhage or bleeding event NCI CTCAE version 4.03 Grade 3 or higher within 4 weeks before randomization.
8. Known risk of intracranial bleeding, such as a brain aneurysm or history of intracranial bleeding within one year prior to randomization.
9. Non-healing wound, ulcer, or bone fracture.
10. Poor organ function as by one or more of the following laboratory parameters:
o Persistent proteinuria of NCI-CTCAE version 4.03 Grade 3 or higher
o Alanine aminotransferase and AST > 3 × upper limit of normal (ULN) if 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 (Cockcroft-Gault formula) or measured creatinine clearance < 40 mL/min.
o Platelet count < 90 × 109/L and absolute neutrophil count (ANC) < 1.0 × 109/L.
o Hemoglobin < 9 g/dL. Transfusion and erythropoietin may be used to reach at least 9 g/dL, but 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 inducer of CYP3A4.
13. Major surgical procedure (minor surgical procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not major surgical procedures) within 14 days of randomization. Patient has significant traumatic injury within 28 days before randomization.
14. History of another primary malignancy that has been diagnosed or required therapy within 3 years before randomization. (The following are exempt from the 3-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.)
15. History of a seizure disorder requiring anti-seizure medication.
16. Metastases to the brain.
17. Patients who are unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
18. QT interval corrected using Fridericia's formula (QTcF) of > 450 msec
19. Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercou

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

Related Trials