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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Sunitinib; Drug: Ripretinib

• Study Type: Interventional
• Enrollment (Actual): 453
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Instituto Medicao Especializado Alexander Fleming
  • Cordoba
    • Córdoba, Cordoba, Argentina, X5000JHQ
      • Sanatorio Allende
• Australia
  • Woolloongabba, Australia
    • Princess Alexandara Hospital
  • New South Wales
    • Albury, New South Wales, Australia
      • Border Medical Oncology Research Unit
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia
      • Princess Alexandra Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Ashford Cancer Centre Research
    • Kurralta Park, South Australia, Australia
      • Ashford Cancer Centre Research
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Belgium
  • Bruxelles, Belgium
    • Institut Jules Bordet
  • Leuven, Belgium
    • UZ Leuven
• Canada
  • Québec, Canada
    • Hôpital Maisonneuve-Rosemont
  • Alberta
    • Edmonton, Alberta, Canada
      • Cross Cancer Institute
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • CancerCare Manitoba
  • Ontario
    • Hamilton, Ontario, Canada
      • Juravinski Cancer Centre
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M5G 2C1
      • Princess Margaret Cancer Centre
• Chile
  • Santiago, Chile
    • Clinica San Carlos de Apoquindo Red Salud UC Christs
• Czechia
  • Prague, Czechia
    • Fakultni Nemocnice V Motole
• France
  • Bordeaux, France
    • Institut Bergonnié
  • Dijon, France
    • Centre Georges Francois Leclerc
  • Lille Cedex, France
    • Centre Oscar Lambret
  • Lyon, France
    • Centre Léon Bérard
  • Marseille, France
    • Hôpital La Timone
  • Marseille, France
    • IPC
  • Paris, France
    • IGR
  • Poitiers, France
    • CHU Poitiers-Hopital la Miletrie
  • Saint Herblain, France
    • ICO - Site René Gauducheau
• Germany
  • Berlin, Germany
    • HELIOS Klinikum Berlin-Buch
  • Dresden, Germany
    • Technische Universität Dresden
  • Essen, Germany
    • West German Cancer Center
• Hungary
  • Budapest, Hungary
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Debrecen, Hungary
    • Debreceni Egyetem
• Israel
  • Be'er Ya'akov, Israel
    • Shamir Medical Center (Assaf Harofeh)
  • Petah Tikva, Israel
    • Rabin Medical Cente
  • Tel Aviv, Israel
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy
    • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
  • Meldola, Italy
    • stituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
  • Milan, Italy
    • Fondazione Irccs Istituto Nazionale Dei Tumori
  • Padova, Italy
    • Iov - Istituto Oncologico Veneto Irccs
  • Palermo, Italy
    • Universita Degli Studi Di Palermo
  • Rome, Italy
    • Università Campus Bio-Medico di Roma
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Suwon, Korea, Republic of
    • Ajou University Hospital
• Netherlands
  • Amsterdam, Netherlands
    • The Netherlands Cancer Institute
  • Amsterdam, Netherlands
    • Antoni van Leeuwenhoek
  • Groningen, Netherlands
    • University Medical Center Groningen
  • Leiden, Netherlands
    • Leiden University Medical Centre
• Norway
  • Oslo, Norway
    • Oslo University Hospital
• Poland
  • Warsaw, Poland
    • Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital de La Santa Creu I Sant Pau
  • Bilbao, Spain
    • Hospital De Basurto
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain
    • Hospital Universitario HM Madrid Sanchinarro
  • Malaga, Spain
    • Hospital Clinico Universitario Virgen de la Victoria
  • Sevilla, Spain
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain
    • Instituto Valenciano de Oncología,
  • Vigo, Spain
    • Complejo Hospitalario Universitario de Vigo
• Sweden
  • Solna, Sweden
    • Karolinska Universitetssjukhuset
• Switzerland
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois, Fondation du Centre Pluridisciplinaire d'Oncologi
  • Zurich, Switzerland
    • Universitaetsspital Zuerich, Klinik fuer Onkologie
• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital,
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • National Chen Kung University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan County
    • Linkou, Taoyuan County, Taiwan
      • Chang Gung Memorial Hospital
• United Kingdom
  • Glasgow, United Kingdom
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom
    • St James's University Hospital
  • London, United Kingdom
    • University College London Hospitals
  • London, United Kingdom
    • Royal Marsden Hospital - Fulham
  • Sheffield, United Kingdom
    • Weston Park Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • La Jolla, California, United States, 92103
      • University of California San Diego Medical Center
    • Los Angeles, California, United States, 90024
      • UCLA Hematology Oncology Center - Main Site
    • Stanford, California, United States, 94305
      • Stanford Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavillion
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Smilow Cancer Hospital at Yale
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Cancer Institute at MedStar Washington Hospital Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health, Inc.
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
    • Orlando, Florida, United States, 32806
      • Orlando Health UF Health Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30332
      • Winship Cancer Institute
    • Sandy Springs, Georgia, United States, 30342
      • Georgia Cancer Specialists
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Simon Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Norton Cancer Institute, Audubon Hospital Campus
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center-Fairview
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Siteman Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center-Montefiore Medical Park
    • Buffalo, New York, United States, 43606
      • Roswell Park Cancer Institute
    • Lake Success, New York, United States, 11042
      • The Monter Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Solove Research Institute
    • Toledo, Ohio, United States, 43606
      • University of Toledo
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University Center for Health and Healing
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Clinic
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital-Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ripretinib; Ripretinib (150 mg) once a day continuous dosing for 6-week (42 days) cycles	Drug: Ripretinib; Oral KIT/PDGFRA kinase inhibitor; Other Names: DCC-2618
Active Comparator: Sunitinib; Sunitinib (50 mg) once a day in 6-week (42 days) cycles with 4 weeks continuous dosing followed by 2 week break.	Drug: Sunitinib; Oral receptor tyrosine kinase (RTK) inhibitor; Other Names: Sutent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	From date of randomization until death due to any cause (up to 3.33 years)

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals LLC

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Deciphera Company Website

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2019
• Primary Completion (Actual): September 1, 2021
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 13, 2018
• First Submitted That Met QC Criteria: September 14, 2018
• First Posted (Actual): September 17, 2018

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: DCC-2618-03-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No