This is a 2-arm, randomized, open-label, international, multicenter study comparing the efficacy of ripretinib to sunitinib in GIST patients who progressed on or were intolerant to first-line anticancer treatment with imatinib. Approximately 426 patients will be randomized in a 1:1 ratio to ripretinib 150 mg once daily (continuous dosing for 6 week cycles) or sunitinib 50 mg once daily (6 week cycles, 4 weeks on, 2 weeks off).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Patients ≥ 18 years of age at the time of informed consent.
2. Histologic diagnosis of GIST and must be able to provide an archival tumor tissue sample, otherwise, a fresh biopsy is required.
3. Molecular pathology report must be available. If molecular pathology report is not available or insufficient, an archival tumor tissue sample or fresh biopsy is required for mutation status confirmation by the central laboratory prior to randomization.
4. Patients must have progressed on imatinib or have documented intolerance to imatinib.
5. Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of ≤ 2 at screening.
6. Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening and negative pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug.
7. Patients of reproductive potential must agree to follow the contraception requirements outlined in the study protocol.
8. Patients must have at least 1 measurable lesion according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 (non nodal lesions must be ≥ 1.0 cm in the long axis or ≥ double the slice thickness in the long axis) within 21 days prior to the first dose of study drug.
9. Adequate organ function and bone marrow reserve as indicated by the central laboratory assessments performed at screening.
10. Resolution of all toxicities from prior therapy to ≤ Grade 1 (or patient baseline) within 1 week prior to the first dose of study drug (excluding alopecia and ≤ Grade 3 clinically asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).
11. The patient is capable of understanding and complying with the protocol and the patient has signed the informed consent document. Signed informed consent form (ICF) must be obtained before any study-specific procedures are performed and the patient must agree to not participate in any other interventional clinical trial while on treatment in this clinical trial. Participation in a noninterventional study (including observational studies) is permitted.
Exclusion Criteria:
1. Treatment with any other line of therapy in addition to imatinib for advanced GIST. Imatinib-containing combination therapy in the first-line setting is not allowed.
2. Patients with a prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible.
3. Patient has known active central nervous system metastases.
4. New York Heart Association class II-IV heart disease, myocardial infarction within 6 months of cycle 1 day 1, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
5. Left ventricular ejection fraction (LVEF) \< 50% at screening.
6. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
7. Venous thrombotic events (e.g. deep vein thrombosis) or pulmonary arterial events (e.g. pulmonary embolism) within 1 month before the first dose of study drug. Patients on stable anticoagulation therapy for at least one month are eligible.
8. 12-lead ECG demonstrating QT interval corrected (QTc) by Fridericia's formula \> 450 ms in males or \> 470 ms in females at screening or history of long QTc syndrome
9. Use of known substrates or inhibitors of breast cancer resistance protein (BCRP) transporters within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug.
10. Major surgeries (e.g. abdominal laparotomy) within 4 weeks of the first dose of study drug. All major surgical wounds must be healed and free of infection or dehiscence before the first dose of study drug.
11. Any other clinically significant comorbidities.
12. Known human immunodeficiency virus or hepatitis C infection only if the patient is taking medications that are excluded per protocol, active hepatitis B, or active hepatitis C infection.
13. If female, the patient is pregnant or lactating.
14. Known allergy or hypersensitivity to any component of the study drug.
15. Gastrointestinal abnormalities including but not limited to:
* inability to take oral medication
* malabsorption syndromes
* requirement for intravenous (IV) alimentation
16. Any active bleeding excluding hemorrhoidal or gum bleeding.
Primary outcome measure(s)
Progression Free Survival (PFS) in the KIT Exon 11 Intent to Treat (ITT) Population — From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years) PFS is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the independent radiologic review using modified RECIST Version 1.1-(mRECIST 1.1) GIST specific, or death due to any cause. Per mRECIST 1.1, progression was defined using mRECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Progression Free Survival (PFS) in the All Patient (AP) Intent to Treat (ITT) Population — From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years) PFS is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the independent radiologic review using modified RECIST Version 1.1-(mRECIST 1.1) Gastrointestinal stromal tumor (GIST) specific, or death due to any cause. Per mRECIST 1.1, progression was defined using mRECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Trial sites (121)
Facility
City
Region
Status
Mayo Clinic Scottsdale
Scottsdale
Arizona
University of California San Diego Medical Center
La Jolla
California
UCLA Hematology Oncology Center - Main Site
Los Angeles
California
Stanford Medicine
Stanford
California
University of Colorado Hospital - Anschutz Cancer Pavillion
Aurora
Colorado
Rocky Mountain Cancer Centers
Denver
Colorado
Smilow Cancer Hospital at Yale
New Haven
Connecticut
Washington Cancer Institute at MedStar Washington Hospital Center
Washington D.C.
District of Columbia
Mayo Clinic Florida
Jacksonville
Florida
Sylvester Comprehensive Cancer Center
Miami
Florida
Miami Cancer Institute at Baptist Health, Inc.
Miami
Florida
Orlando Health UF Health Cancer Center
Orlando
Florida
Moffitt Cancer Center
Tampa
Florida
Winship Cancer Institute
Atlanta
Georgia
Georgia Cancer Specialists
Sandy Springs
Georgia
Northwestern Memorial Hospital
Chicago
Illinois
University of Chicago Medical Center
Chicago
Illinois
IU Simon Cancer Center
Indianapolis
Indiana
University of Iowa Hospital and Clinics
Iowa City
Iowa
Norton Cancer Institute, Audubon Hospital Campus
Louisville
Kentucky
Johns Hopkins Hospital
Baltimore
Maryland
Dana Farber Cancer Institute
Boston
Massachusetts
Henry Ford Health System
Detroit
Michigan
University of Minnesota Medical Center-Fairview
Minneapolis
Minnesota
Mayo Clinic
Rochester
Minnesota
Washington University School of Medicine - Siteman Cancer Center
St Louis
Missouri
Rutgers Cancer Institute
New Brunswick
New Jersey
Roswell Park Cancer Institute
Buffalo
New York
The Monter Cancer Center
Lake Success
New York
Memorial Sloan Kettering Cancer Center
New York
New York
Montefiore Medical Center-Montefiore Medical Park
The Bronx
New York
Duke University Medical Center
Durham
North Carolina
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Solove Research Institute
Columbus
Ohio
University of Toledo
Toledo
Ohio
Stephenson Cancer Center
Oklahoma City
Oklahoma
Oregon Health & Science University Center for Health and Healing
Portland
Oregon
Fox Chase Cancer Center
Philadelphia
Pennsylvania
Henry-Joyce Cancer Clinic
Nashville
Tennessee
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas
Texas
University of Texas MD Anderson Cancer Center
Houston
Texas
+ 81 more sites — see the full list on the official registry below.
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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