A Study of DCC-2618 vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib (intrigue)

• ClinicalTrials.gov Identifier: NCT03673501
• Recruitment Status: Unknown
• First Posted: September 17, 2018
• Last Update Posted: January 6, 2021
• Sponsor: Deciphera Pharmaceuticals LLC
• Information provided by (Responsible Party): Deciphera Pharmaceuticals LLC

Study Description

Brief Summary:

This is a 2-arm, randomized, open-label, international, multicenter study comparing the efficacy of DCC-2618 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 DCC-2618 150 mg once daily (QD) (continuous dosing for 6 week cycles) or sunitinib 50 mg QD (6 week cycles, 4 weeks on, 2 weeks off).

Condition or disease	Intervention/treatment	Phase
Gastrointestinal Stromal Tumors	Drug: DCC-2618; Drug: Sunitinib	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 426 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Interventional, Randomized, Multicenter, Open-Label Study of DCC-2618 vs Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumors After Treatment With Imatinib
• Actual Study Start Date: February 11, 2019
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: March 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: DCC-2618; 150 mg QD DCC-2618	Drug: DCC-2618; Oral KIT/PDGFRA kinase inhibitor; Other Name: ripretinib
Active Comparator: sunitinib; 50 mg QD sunitinib	Drug: Sunitinib; Oral receptor tyrosine kinase (RTK) inhibitor; Other Name: Sutent

Outcome Measures

Primary Outcome Measures :

1. Progression free survival (PFS) [ Time Frame: 30 months ]
   PFS Based on independent radiologic review using modified RECIST

Secondary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: 30 months ]
   Objective response rate as determined by confirmed CR + confirmed PR by independent radiologic review
2. Overall Survival (OS) [ Time Frame: 30 months ]
   Measure of overall survival

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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) 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 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 [CPK] 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 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.

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States, 85259

United States, California

University of California San Diego Medical Center

La Jolla, California, United States, 92103

UCLA Hematology Oncology Center - Main Site

Los Angeles, California, United States, 90024

Stanford Medicine

Stanford, California, United States, 94305

United States, Colorado

University of Colorado Hospital - Anschutz Cancer Pavillion

Aurora, Colorado, United States, 80045

Rocky Mountain Cancer Centers

Denver, Colorado, United States, 80220

United States, Connecticut

Smilow Cancer Hospital at Yale

New Haven, Connecticut, United States, 06511

United States, District of Columbia

Washington Cancer Institute at MedStar Washington Hospital Center

Washington, District of Columbia, United States, 20010

United States, Florida

Mayo Clinic Florida

Jacksonville, Florida, United States, 32224

Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, United States, 33176

Orlando Health UF Health Cancer Center

Orlando, Florida, United States, 32806

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Georgia

Winship Cancer Institute

Atlanta, Georgia, United States, 30332

Georgia Cancer Specialists

Sandy Springs, Georgia, United States, 30342

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Indiana

IU Simon Cancer Center

Indianapolis, Indiana, United States, 46202

United States, Iowa

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States, 52242

United States, Kentucky

Norton Cancer Institute, Audubon Hospital Campus

Louisville, Kentucky, United States, 40241

United States, Maryland

Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

Henry Ford Health System

Detroit, Michigan, United States, 48202

United States, Minnesota

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, United States, 55455

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University School of Medicine - Siteman Cancer Center

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Rutgers Cancer Institute

New Brunswick, New Jersey, United States, 08901

United States, New York

Montefiore Medical Center-Montefiore Medical Park

Bronx, New York, United States, 10467

Roswell Park Cancer Institute

Buffalo, New York, United States, 43606

The Monter Cancer Center

Lake Success, New York, United States, 11042

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

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

Columbus, Ohio, United States, 43210

University of Toledo

Toledo, Ohio, United States, 43606

United States, Oklahoma

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Oregon Health & Science University Center for Health and Healing

Portland, Oregon, United States, 97239

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, Tennessee

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States, 75246

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Virginia

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States, 23298

United States, Washington

University of Washington Medical Center

Seattle, Washington, United States, 98195

United States, Wisconsin

Froedtert Hospital-Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Argentina

Sanatorio Allende

Córdoba, Cordoba, Argentina, X5000JHQ

Instituto Medicao Especializado Alexander Fleming

Buenos Aires, Argentina

Australia, New South Wales

Border Medical Oncology Research Unit

Albury, New South Wales, Australia

Prince of Wales Hospital

Randwick, New South Wales, Australia, 2031

Australia, Queensland

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Australia, South Australia

Ashford Cancer Centre Research

Kurralta Park, South Australia, Australia, 5037

Ashford Cancer Centre Research

Kurralta Park, South Australia, Australia

Australia, Victoria

The Alfred Hospital

Melbourne, Victoria, Australia, 3004

Australia

Princess Alexandara Hospital

Woolloongabba, Australia

Belgium

Institut Jules Bordet

Bruxelles, Belgium

UZ Leuven

Leuven, Belgium

Canada, Alberta

Cross Cancer Institute

Edmonton, Alberta, Canada

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Canada, Ontario

Juravinski Cancer Centre

Hamilton, Ontario, Canada

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2C1

Canada

Hopital Maisonneuve-Rosemont

Québec, Canada

Chile

Clinica San Carlos de Apoquindo Red Salud UC Christs

Santiago, Chile

Czechia

Fakultni nemocnice v Motole

Prague, Czechia

France

Institut Bergonnié

Bordeaux, France

Centre Georges François Leclerc

Dijon, France

Centre Oscar Lambret

Lille Cedex, 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

Germany

HELIOS Klinikum Berlin-Buch

Berlin, Germany

Technische Universitat Dresden

Dresden, Germany

West German Cancer Center

Essen, Germany

Hungary

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, Hungary

Debreceni Egyetem

Debrecen, Hungary

Israel

Shamir Medical Center (Assaf Harofeh)

Be'er Ya'akov, Israel

Rabin Medical Cente

Petah Tikva, Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, Israel

Italy

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

Padova, Italy

Universita degli Studi di Palermo

Palermo, Italy

Università Campus Bio-Medico di Roma

Rome, Italy

Korea, Republic of

Asan Medical Center

Seoul, Korea, Republic of

Samsung Medical Center

Seoul, Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of

Ajou University Hospital

Suwon, Korea, Republic of

Netherlands

Antoni van Leeuwenhoek

Amsterdam, Netherlands

The Netherlands Cancer Institute

Amsterdam, Netherlands

University Medical Center Groningen

Groningen, Netherlands

Leiden University Medical Centre

Leiden, Netherlands

Norway

Oslo University Hospital

Oslo, Norway

Poland

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, Poland

Singapore

National Cancer Centre

Singapore, Singapore, 169610

Spain

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

Malaga, Spain

Hospital Universitario Virgen del Rocio

Sevilla, Spain

Instituto Valenciano de Oncología,

Valencia, Spain

Complejo Hospitalario Universitario de Vigo

Vigo, Spain

Sweden

Karolinska universitetssjukhuset

Solna, Sweden

Switzerland

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

Lausanne, Switzerland

Universitaetsspital Zuerich, Klinik fuer Onkologie

Zurich, Switzerland

Taiwan

Chang Gung Memorial Hospital

Linkou, Taoyuan County, Taiwan

Kaohsiung Chang Gung Memorial Hospital,

Kaohsiung, Taiwan

China Medical University Hospital

Taichung, Taiwan

National Chen Kung University Hospital

Tainan, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

United Kingdom

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

Sponsors and Collaborators

Deciphera Pharmaceuticals LLC

More Information

Additional Information:

Deciphera Company Website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Deciphera Pharmaceuticals LLC
• ClinicalTrials.gov Identifier: NCT03673501
• Other Study ID Numbers: DCC-2618-03-002
• First Posted: September 17, 2018
• Last Update Posted: January 6, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Sunitinib; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action