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

Gastrointestinal Stromal Tumors Clinical Trial

— INTRIGUE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03673501
• Other study ID #: DCC-2618-03-002
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 8, 2019
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: Deciphera Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 453
• Est. completion date: December 2024
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (ß-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.

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• Ripretinib
Oral KIT/PDGFRA kinase inhibitor
• Sunitinib
Oral receptor tyrosine kinase (RTK) inhibitor

Locations

Country	Name	City	State
Argentina	Instituto Medicao Especializado Alexander Fleming	Buenos Aires
Argentina	Sanatorio Allende	Córdoba	Cordoba
Australia	Border Medical Oncology Research Unit	Albury	New South Wales
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	Prince of Wales Hospital	Randwick	New South Wales
Australia	Princess Alexandara Hospital	Woolloongabba
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Institut Jules Bordet	Bruxelles
Belgium	UZ Leuven	Leuven
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Hopital Maisonneuve-Rosemont	Québec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Chile	Clinica San Carlos de Apoquindo Red Salud UC Christs	Santiago
Czechia	Fakultni nemocnice v Motole	Prague
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
Germany	HELIOS Klinikum Berlin-Buch	Berlin
Germany	Technische Universitat Dresden	Dresden
Germany	West German Cancer Center	Essen
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	Debreceni Egyetem	Debrecen
Israel	Shamir Medical Center (Assaf Harofeh)	Be'er Ya'akov
Israel	Rabin Medical Cente	Petah Tikva
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
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
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
Netherlands	Antoni van Leeuwenhoek	Amsterdam
Netherlands	The Netherlands Cancer Institute	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Centre	Leiden
Norway	Oslo University Hospital	Oslo
Poland	Centrum Onkologii-Instytut im. M. Sklodowskiej Curie	Warsaw
Singapore	National Cancer Centre	Singapore
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
Sweden	Karolinska universitetssjukhuset	Solna
Switzerland	Centre Hospitalier Universitaire Vaudois, Fondation du Centre Pluridisciplinaire d'Oncologi	Lausanne
Switzerland	Universitaetsspital Zuerich, Klinik fuer Onkologie	Zurich
Taiwan	Kaohsiung Chang Gung Memorial Hospital,	Kaohsiung
Taiwan	Chang Gung Memorial Hospital	Linkou	Taoyuan County
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Chen Kung University Hospital	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei
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 States	Winship Cancer Institute	Atlanta	Georgia
United States	University of Colorado Hospital - Anschutz Cancer Pavillion	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center-Montefiore Medical Park	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	IU Simon Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	University of California San Diego Medical Center	La Jolla	California
United States	The Monter Cancer Center	Lake Success	New York
United States	UCLA Hematology Oncology Center - Main Site	Los Angeles	California
United States	Norton Cancer Institute, Audubon Hospital Campus	Louisville	Kentucky
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Froedtert Hospital-Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	Rutgers Cancer Institute	New Brunswick	New Jersey
United States	Smilow Cancer Hospital at Yale	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Orlando Health UF Health Cancer Center	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Oregon Health & Science University Center for Health and Healing	Portland	Oregon
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri
United States	Georgia Cancer Specialists	Sandy Springs	Georgia
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	University of Washington Medical Center	Seattle	Washington
United States	Stanford Medicine	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	University of Toledo	Toledo	Ohio
United States	Washington Cancer Institute at MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Deciphera Pharmaceuticals LLC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

•   Deciphera Company Website