Gastrointestinal Stromal TumorsPhase 3INTRIGUENCT03673501
A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib
A Phase 3 study testing Ripretinib and Sunitinib in people with Gastrointestinal Stromal Tumors, run by Deciphera Pharmaceuticals, LLC at 121 sites in 22 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- Ripretinib and Sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 453 participants
- Where
- 121 sitesin 22 countries
- Study dates
- 8 Feb 2019to Dec 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years of age at the time of informed consent.
- Histologic diagnosis of GIST and must be able to provide an archival tumor tissue sample, otherwise, a fresh biopsy is required.
- 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.
- Patients must have progressed on imatinib or have documented intolerance to imatinib.
- Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of ≤ 2 at screening.
- 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.
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- Patients of reproductive potential must agree to follow the contraception requirements outlined in the study protocol.
- 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.
- Adequate organ function and bone marrow reserve as indicated by the central laboratory assessments performed at screening.
- 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).
- 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.
Who cannot join
- 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.
- 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.
- Patient has known active central nervous system metastases.
- 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.
- Left ventricular ejection fraction (LVEF) < 50% at screening.
- Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
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- 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.
- 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
- 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.
- 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.
- Any other clinically significant comorbidities.
- 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.
- If female, the patient is pregnant or lactating.
- Known allergy or hypersensitivity to any component of the study drug.
- Gastrointestinal abnormalities including but not limited to:
- inability to take oral medication
- malabsorption syndromes
- requirement for intravenous (IV) alimentation
- Any active bleeding excluding hemorrhoidal or gum bleeding.
Trial locations and contacts
121 sites in 22 countries.
121 sites in 22 countries
United States43 sites
Winship Cancer Institute
Atlanta, Georgia, 30332
University of Colorado Hospital - Anschutz Cancer Pavillion
Aurora, Colorado, 80045
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 43606
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Chicago Medical Center
Chicago, Illinois, 60637
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Rocky Mountain Cancer Centers
Denver, Colorado, 80220
Henry Ford Health System
Detroit, Michigan, 48202
Duke University Medical Center
Durham, North Carolina, 27710
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
IU Simon Cancer Center
Indianapolis, Indiana, 46202
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242
Mayo Clinic Florida
Jacksonville, Florida, 32224
University of California San Diego Medical Center
La Jolla, California, 92103
The Monter Cancer Center
Lake Success, New York, 11042
UCLA Hematology Oncology Center - Main Site
Los Angeles, California, 90024
Norton Cancer Institute, Audubon Hospital Campus
Louisville, Kentucky, 40241
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Miami Cancer Institute at Baptist Health, Inc.
Miami, Florida, 33176
Froedtert Hospital-Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455
Henry-Joyce Cancer Clinic
Nashville, Tennessee, 37232
Rutgers Cancer Institute
New Brunswick, New Jersey, 08901
Smilow Cancer Hospital at Yale
New Haven, Connecticut, 06511
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Orlando Health UF Health Cancer Center
Orlando, Florida, 32806
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Oregon Health & Science University Center for Health and Healing
Portland, Oregon, 97239
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298
Mayo Clinic
Rochester, Minnesota, 55905
Georgia Cancer Specialists
Sandy Springs, Georgia, 30342
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259
University of Washington Medical Center
Seattle, Washington, 98195
Washington University School of Medicine - Siteman Cancer Center
St Louis, Missouri, 63110
Stanford Medicine
Stanford, California, 94305
Moffitt Cancer Center
Tampa, Florida, 33612
Montefiore Medical Center-Montefiore Medical Park
The Bronx, New York, 10467
University of Toledo
Toledo, Ohio, 43606
Washington Cancer Institute at MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Spain12 sites
Hospital de la Santa Creu i Sant Pau
Barcelona
Hospital Universitari Vall d'Hebron
Barcelona
Hospital de Basurto
Bilbao
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario Clinico San Carlos
Madrid
Hospital Universitario HM Madrid Sanchinarro
Madrid
Hospital Universitario La Paz
Madrid
Hospital Universitario Ramon y Cajal
Madrid
Hospital Clinico Universitario Virgen de la Victoria
Málaga
Hospital Universitario Virgen del Rocio
Seville
Instituto Valenciano de Oncología,
Valencia
Complejo Hospitalario Universitario de Vigo
Vigo
France9 sites
Institut Bergonnié
Bordeaux
Centre Georges François Leclerc
Dijon
Centre Oscar Lambret
Lille
Centre Léon Bérard
Lyon
Hopital La Timone
Marseille
IPC
Marseille
IGR
Paris
CHU Poitiers-Hopital la Miletrie
Poitiers
ICO - Site René Gauducheau
Saint-Herblain
Australia7 sites
Border Medical Oncology Research Unit
Albury, New South Wales
Ashford Cancer Centre Research
Kurralta Park, South Australia, 5037
Ashford Cancer Centre Research
Kurralta Park, South Australia
The Alfred Hospital
Melbourne, Victoria, 3004
Prince of Wales Hospital
Randwick, New South Wales, 2031
Princess Alexandra Hospital
Woolloongabba, Queensland
Princess Alexandara Hospital
Woolloongabba
Canada6 sites
Cross Cancer Institute
Edmonton, Alberta
Juravinski Cancer Centre
Hamilton, Ontario
The Ottawa Hospital Cancer Centre
Ottawa, Ontario
Hopital Maisonneuve-Rosemont
Québec
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C1
CancerCare Manitoba
Winnipeg, Manitoba
Italy6 sites
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
Bologna
stituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
Meldola
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
IOV - Istituto Oncologico Veneto IRCCS
Padova
Universita degli Studi di Palermo
Palermo
Università Campus Bio-Medico di Roma
Rome
Taiwan5 sites
Kaohsiung Chang Gung Memorial Hospital,
Kaohsiung City
Chang Gung Memorial Hospital
Linkou District, Taoyuan County
China Medical University Hospital
Taichung
National Chen Kung University Hospital
Tainan
Taipei Veterans General Hospital
Taipei
United Kingdom5 sites
Beatson West of Scotland Cancer Centre
Glasgow
St James's University Hospital
Leeds
Royal Marsden Hospital - Fulham
London
University College London Hospitals
London
Weston Park Hospital
Sheffield
Netherlands4 sites
Antoni van Leeuwenhoek
Amsterdam
The Netherlands Cancer Institute
Amsterdam
University Medical Center Groningen
Groningen
Leiden University Medical Centre
Leiden
South Korea4 sites
Asan Medical Center
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Ajou University Hospital
Suwon
Germany3 sites
HELIOS Klinikum Berlin-Buch
Berlin
Technische Universitat Dresden
Dresden
West German Cancer Center
Essen
Israel3 sites
Shamir Medical Center (Assaf Harofeh)
Be’er Ya‘aqov
Rabin Medical Cente
Petah Tikva
Tel-Aviv Sourasky Medical Center
Tel Aviv
Argentina2 sites
Instituto Medicao Especializado Alexander Fleming
Buenos Aires
Sanatorio Allende
Córdoba, Córdoba Province, X5000JHQ
Hungary2 sites
Magyar Honvedseg Egeszsegugyi Kozpont
Budapest
Debreceni Egyetem
Debrecen
Switzerland2 sites
Centre Hospitalier Universitaire Vaudois, Fondation du Centre Pluridisciplinaire d'Oncologi
Lausanne
Universitaetsspital Zuerich, Klinik fuer Onkologie
Zurich
About this study
Official title: A Phase 3, Interventional, Randomized, Multicenter, Open-Label Study of Ripretinib vs Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor (GIST) After Treatment With Imatinib
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
- Being tested
- Ripretinib, Sunitinib
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RipretinibDrug
Also called DCC-2618
Oral KIT/PDGFRA kinase inhibitor
SunitinibDrug
Also called Sutent
Oral receptor tyrosine kinase (RTK) inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Ripretinib | Experimental | Ripretinib (150 mg) once a day continuous dosing for 6-week (42 days) cycles Receives: Drug: Ripretinib |
| Sunitinib | Active comparator | Sunitinib (50 mg) once a day in 6-week (42 days) cycles with 4 weeks continuous dosing followed by 2 week break. Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) in the KIT Exon 11 Intent to Treat (ITT) Population
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.
Measured: From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)
Progression Free Survival (PFS) in the All Patient (AP) Intent to Treat (ITT) Population
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.
Measured: From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)
Secondary outcomes (4)
Objective Response Rate (ORR) in the KIT Exon 11 Intent to Treat (ITT) Population Population
ORR was defined as the proportion of patients with confirmed complete response (CR) + confirmed partial response (PR) based on independent radiologic review using modified RECIST (mRECIST) criteria as best overall response. Per mRECIST 1.1 criteria, complete response is defined as disappearance of all target lesions; partial response is defined as >=30% decrease in the sum of the longest diameter of target lesions.
Measured: From confirmed CR or PR to disease progression (up to 1.74 years)
Objective Response Rate (ORR) in the All Patient (AP) Intent to Treat (ITT) Population
ORR was defined as the proportion of patients with confirmed complete response (CR) + confirmed partial response (PR) based on independent radiologic review using modified RECIST (mRECIST) criteria as best overall response. Per mRECIST 1.1 criteria, complete response is defined as disappearance of all target lesions; partial response is defined as >=30% decrease in the sum of the longest diameter of target lesions.
Measured: From confirmed CR or PR to disease progression (up to 1.74 years)
Overall Survival (OS) in the KIT Exon 11 Intent to Treat (ITT) Population
OS was defined as the time from the date of randomization until death due to any cause.
Measured: From date of randomization until death due to any cause (up to 3.33 years)
Overall Survival (OS) in the All Patient (AP) Intent to Treat (ITT) Population
OS was defined as the time from the date of randomization until death due to any cause.
Measured: From date of randomization until death due to any cause (up to 3.33 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2018
- Study start8 Feb 2019
- Primary completion1 Sep 2021
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 453 participants (actual)
Sponsor and investigators
- Lead sponsor
- Deciphera Pharmaceuticals, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03673501
- Sponsor's protocol ID
- DCC-2618-03-002
- Acronym
- INTRIGUE
- Status last verified
- Sep 2026
- First submitted
- 13 Sep 2018
- Last updated
- 16 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40408605Heinrich MC, Jones RL, George S, Gelderblom H, Schoffski P, 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, Reichmann W, Sprott K, Achour H, Sherman ML, Ruiz-Soto R, Blay JY, Bauer S. Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial. Nat Med. 2024 Feb;30(2):498-506. doi: 10.1038/s41591-023-02734-5. Epub 2024 Jan 5.
PubMed 38182785Gelderblom 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.
PubMed 37598656Bauer 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.
PubMed 35947817Nemunaitis 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.
PubMed 31755321