Clinical trial NCT03673501: A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Gastrointestinal Stromal Tumors
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2018-09-17
Enrollment: 453
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Progression Free Survival (PFS) in the KIT Exon 11 Intent to Treat (ITT) Population
timeFrame: From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)
measure: Progression Free Survival (PFS) in the All Patient (AP) Intent to Treat (ITT) Population
timeFrame: From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years)
Secondary outcomes:
measure: Objective Response Rate (ORR) in the KIT Exon 11 Intent to Treat (ITT) Population Population
timeFrame: From confirmed CR or PR to disease progression (up to 1.74 years)
measure: Objective Response Rate (ORR) in the All Patient (AP) Intent to Treat (ITT) Population
timeFrame: From confirmed CR or PR to disease progression (up to 1.74 years)
measure: Overall Survival (OS) in the KIT Exon 11 Intent to Treat (ITT) Population
timeFrame: From date of randomization until death due to any cause (up to 3.33 years)
measure: Overall Survival (OS) in the All Patient (AP) Intent to Treat (ITT) Population
timeFrame: From date of randomization until death due to any cause (up to 3.33 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology Oncology Center - Main Site
state: California
city: Stanford
country: United States
facility: Stanford Medicine
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavillion
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale
state: Connecticut
city: Washington
country: United States
facility: Washington Cancer Institute at MedStar Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health, Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Health UF Health Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Sandy Springs
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: IU Simon Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute, Audubon Hospital Campus
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center-Fairview
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center-Montefiore Medical Park
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: The Monter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Solove Research Institute
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University Center for Health and Healing
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital-Medical College of Wisconsin
state: Wisconsin
city: Córdoba
country: Argentina
facility: Sanatorio Allende
state: Cordoba
city: Buenos Aires
country: Argentina
facility: Instituto Medicao Especializado Alexander Fleming
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Woolloongabba
country: Australia
facility: Princess Alexandara Hospital
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: UZ Leuven
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Québec
country: Canada
facility: Hopital Maisonneuve-Rosemont
city: Santiago
country: Chile
facility: Clinica San Carlos de Apoquindo Red Salud UC Christs
city: Prague
country: Czechia
facility: Fakultni nemocnice v Motole
city: Bordeaux
country: France
facility: Institut Bergonnié
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille Cedex
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hopital La Timone
city: Marseille
country: France
facility: IPC
city: Paris
country: France
facility: IGR
city: Poitiers
country: France
facility: CHU Poitiers-Hopital la Miletrie
city: Saint Herblain
country: France
facility: ICO - Site René Gauducheau
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Dresden
country: Germany
facility: Technische Universitat Dresden
city: Essen
country: Germany
facility: West German Cancer Center
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
city: Be'er Ya'akov
country: Israel
facility: Shamir Medical Center (Assaf Harofeh)
city: Petah Tikva
country: Israel
facility: Rabin Medical Cente
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
city: Meldola
country: Italy
facility: stituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS
city: Palermo
country: Italy
facility: Universita degli Studi di Palermo
city: Rome
country: Italy
facility: Università Campus Bio-Medico di Roma
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Warsaw
country: Poland
facility: Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario HM Madrid Sanchinarro
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología,
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo
city: Solna
country: Sweden
facility: Karolinska universitetssjukhuset
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois, Fondation du Centre Pluridisciplinaire d'Oncologi
city: Zurich
country: Switzerland
facility: Universitaetsspital Zuerich, Klinik fuer Onkologie
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital
state: Taoyuan County
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital,
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Chen Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham
city: London
country: United Kingdom
facility: University College London Hospitals
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
Study officials:
References:
citation: 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.
citation: 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.