A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib

NCT ID: NCT03673501

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 453 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-08
• Study Completion Date: 2025-12-31

Brief Summary

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).

Conditions

Gastrointestinal Stromal Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ripretinib

Ripretinib (150 mg) once a day continuous dosing for 6-week (42 days) cycles

Group Type: EXPERIMENTAL

Ripretinib

Intervention Type: DRUG

Oral KIT/PDGFRA kinase inhibitor

Sunitinib

Sunitinib (50 mg) once a day in 6-week (42 days) cycles with 4 weeks continuous dosing followed by 2 week break.

Group Type: ACTIVE_COMPARATOR

Sunitinib

Intervention Type: DRUG

Oral receptor tyrosine kinase (RTK) inhibitor

Interventions

Ripretinib

Oral KIT/PDGFRA kinase inhibitor

Intervention Type: DRUG

Sunitinib

Oral receptor tyrosine kinase (RTK) inhibitor

Intervention Type: DRUG

Other Intervention Names

DCC-2618; Sutent

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deciphera Pharmaceuticals, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

University of California San Diego Medical Center

La Jolla, California, United States

UCLA Hematology Oncology Center - Main Site

Los Angeles, California, United States

Stanford Medicine

Stanford, California, United States

University of Colorado Hospital - Anschutz Cancer Pavillion

Aurora, Colorado, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Smilow Cancer Hospital at Yale

New Haven, Connecticut, United States

Washington Cancer Institute at MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, United States

Orlando Health UF Health Cancer Center

Orlando, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Winship Cancer Institute

Atlanta, Georgia, United States

Georgia Cancer Specialists

Sandy Springs, Georgia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

IU Simon Cancer Center

Indianapolis, Indiana, United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Norton Cancer Institute, Audubon Hospital Campus

Louisville, Kentucky, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, United States

Rutgers Cancer Institute

New Brunswick, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

The Monter Cancer Center

Lake Success, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Montefiore Medical Center-Montefiore Medical Park

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

University of Toledo

Toledo, Ohio, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Oregon Health & Science University Center for Health and Healing

Portland, Oregon, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

University of Washington Medical Center

Seattle, Washington, United States

Froedtert Hospital-Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Sanatorio Allende

Córdoba, Córdoba Province, Argentina

Instituto Medicao Especializado Alexander Fleming

Buenos Aires, , Argentina

Border Medical Oncology Research Unit

Albury, New South Wales, Australia

Prince of Wales Hospital

Randwick, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Ashford Cancer Centre Research

Kurralta Park, South Australia, Australia

Ashford Cancer Centre Research

Kurralta Park, South Australia, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Princess Alexandara Hospital

Woolloongabba, , Australia

Institut Jules Bordet

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

Cross Cancer Institute

Edmonton, Alberta, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Hopital Maisonneuve-Rosemont

Québec, , Canada

Clinica San Carlos de Apoquindo Red Salud UC Christs

Santiago, , Chile

Fakultni nemocnice v Motole

Prague, , Czechia

Institut Bergonnié

Bordeaux, , France

Centre Georges François Leclerc

Dijon, , France

Centre Oscar Lambret

Lille, , France

Centre Léon Bérard

Lyon, , France

Hopital La Timone

Marseille, , France

IPC

Marseille, , France

IGR

Paris, , France

CHU Poitiers-Hopital la Miletrie

Poitiers, , France

ICO - Site René Gauducheau

Saint-Herblain, , France

HELIOS Klinikum Berlin-Buch

Berlin, , Germany

Technische Universitat Dresden

Dresden, , Germany

West German Cancer Center

Essen, , Germany

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, , Hungary

Debreceni Egyetem

Debrecen, , Hungary

Shamir Medical Center (Assaf Harofeh)

Be’er Ya‘aqov, , Israel

Rabin Medical Cente

Petah Tikva, , Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, , Italy

stituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

Meldola, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

IOV - Istituto Oncologico Veneto IRCCS

Padua, , Italy

Universita degli Studi di Palermo

Palermo, , Italy

Università Campus Bio-Medico di Roma

Rome, , Italy

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

The Netherlands Cancer Institute

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Leiden University Medical Centre

Leiden, , Netherlands

Oslo University Hospital

Oslo, , Norway

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, , Poland

National Cancer Centre

Singapore, , Singapore

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Ajou University Hospital

Suwon, , South Korea

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital de Basurto

Bilbao, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Clinico San Carlos

Madrid, , Spain

Hospital Universitario HM Madrid Sanchinarro

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Instituto Valenciano de Oncología,

Valencia, , Spain

Complejo Hospitalario Universitario de Vigo

Vigo, , Spain

Karolinska universitetssjukhuset

Solna, , Sweden

Centre Hospitalier Universitaire Vaudois, Fondation du Centre Pluridisciplinaire d'Oncologi

Lausanne, , Switzerland

Universitaetsspital Zuerich, Klinik fuer Onkologie

Zurich, , Switzerland

Chang Gung Memorial Hospital

Linkou District, Taoyuan County, Taiwan

Kaohsiung Chang Gung Memorial Hospital,

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Chen Kung University Hospital

Tainan City, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

St James's University Hospital

Leeds, , United Kingdom

Royal Marsden Hospital - Fulham

London, , United Kingdom

University College London Hospitals

London, , United Kingdom

Weston Park Hospital

Sheffield, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Canada; Chile; Czechia; France; Germany; Hungary; Israel; Italy; Netherlands; Norway; Poland; Singapore; South Korea; Spain; Sweden; Switzerland; Taiwan; United Kingdom

References

Heinrich MC, Blay JY, Gelderblom H, George S, Schoffski P, von Mehren M, Zalcberg JR, Jones RL, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Boye K, Goldstein D, Sanchez C, Siontis BL, Cox P, Davis E, Sherman ML, Ruiz-Soto R, Bauer S. Updated Overall Survival and Long-Term Safety With Ripretinib Versus Sunitinib in Patients With GI Stromal Tumor: Final Overall Survival Analysis From INTRIGUE. J Clin Oncol. 2025 Jul 10;43(20):2239-2244. doi: 10.1200/JCO-24-02818. Epub 2025 May 23.

Reference Type: DERIVED

PMID: 40408605 (View on PubMed)

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Reference Type: DERIVED

PMID: 38182785 (View on PubMed)

Gelderblom H, Jones RL, Blay JY, George S, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Siontis BL, Goldstein D, Boye K, Sanchez C, Steeghs N, Rutkowski P, Druta M, Serrano C, Somaiah N, Chi P, Harrow B, Becker C, Reichmann W, Sherman ML, Ruiz-Soto R, Heinrich MC, Bauer S; INTRIGUE investigators. Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study. Eur J Cancer. 2023 Oct;192:113245. doi: 10.1016/j.ejca.2023.113245. Epub 2023 Jul 20.

Reference Type: DERIVED

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Bauer S, Jones RL, Blay JY, Gelderblom H, George S, Schoffski P, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Su Y, Meade J, Wang T, Sherman ML, Ruiz-Soto R, Heinrich MC. Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Dec 1;40(34):3918-3928. doi: 10.1200/JCO.22.00294. Epub 2022 Aug 10.

Reference Type: DERIVED

PMID: 35947817 (View on PubMed)

Nemunaitis J, Bauer S, Blay JY, Choucair K, Gelderblom H, George S, Schoffski P, Mehren MV, Zalcberg J, Achour H, Ruiz-Soto R, Heinrich MC. Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib. Future Oncol. 2020 Jan;16(1):4251-4264. doi: 10.2217/fon-2019-0633. Epub 2019 Nov 22.

Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.deciphera.com

Deciphera Company Website

Other Identifiers

DCC-2618-03-002

Identifier Type: -

Identifier Source: org_study_id