A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib
- Registration Number
- NCT05734105
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
This is a Phase 3, 2-arm, randomized, open-label, global, multicenter study comparing the efficacy of ripretinib to sunitinib in participants with GIST who progressed on first-line treatment with imatinib, harbor co-occurring KIT exons 11+17/18 mutations, and are without KIT exon 9, 13, or 14 mutations. Upon disease progression as determined by an independent radiologic review, participants randomized to sunitinib will be given the option to either crossover to receive ripretinib 150 mg QD or discontinue sunitinib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 54
- Male or female ≥18 years of age.
- Histologic diagnosis of GIST with co-occurring KIT exons 11+17/18 mutations confirmed by ctDNA sample.
- Participants must have advanced GIST and radiologic progression on imatinib treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2 at screening.
- Female participants of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug.
- Participants of reproductive potential must agree to follow contraception requirements.
- Participants must have at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug.
- Adequate organ function and bone marrow reserve based on laboratory assessments performed at screening.
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History of KIT exon 9 mutation or detection of KIT exon 9, 13, or 14 mutations in a ctDNA sample.
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Has known active central nervous system metastases.
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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.
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Use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A prior to the first dose of study drug, and consumption of grapefruit or grapefruit juice within 14 days prior to the first dose of study drug.
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Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug.
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Known human immunodeficiency virus or hepatitis C infection only if the participant is taking medications that are excluded per protocol, acute or chronic hepatitis B, or acute or chronic hepatitis C infection.
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Gastrointestinal abnormalities including, but not limited to:
- inability to take oral medication
- malabsorption syndromes
- requirement for intravenous alimentation
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Any active bleeding excluding hemorrhoidal or gum bleeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sunitinib Sunitinib 50 mg QD of sunitinib (4×12.5 mg capsules) will be dosed in 42-day cycles. Sunitinib will be given continuously for 4 weeks with a 2-week break. Ripretinib Ripretinib 150 mg QD of ripretinib (3×50 mg tablets) will be dosed continuously in repeated 42-day cycles.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Up to end of treatment; up to approximately 48 months The time from randomization until documented progressive disease (PD) based on IRR per mRECIST or death due to any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to end of treatment; up to approximately 48 months Compare ORR by IRR of ripretinib vs sunitinib using mRECIST
Overall Survival (OS) Up to approximately 48 months Compare OS of ripretinib vs sunitinib
Trial Locations
- Locations (64)
U.O.C. Oncologia Medica
🇮🇹Palermo, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Instituto Valenciano de Oncologia - IVO
🇪🇸Valencia, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
M Health Fairview University of Minnesota Medical Center
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Northwell Health Cancer Institute/ R.J. Zuckerberg Cancer Center
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
CEPEN - Centro de Pesquisa e Ensino em Saude de Santa Catarina
🇧🇷Florianópolis, Santa Catarina, Brazil
Hospital de Cancer de Barretos - Fundacao Pio XII
🇧🇷Barretos, Sao Paulo, Brazil
Hospital Sirio-Libanes
🇧🇷São Paulo, Sao Paulo, Brazil
Hospital 9 de Julho
🇧🇷São Paulo, SP, Brazil
INCA - Instituto Nacional de Cancer
🇧🇷Rio De Janeiro, Brazil
AC Camargo Câncer Center
🇧🇷São Paulo, Brazil
Arthur J.E. Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
University Health Network, Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
Clínica San Carlos De Apoquindo Red Salud UC Christus
🇨🇱Las Condes, RM, Chile
Centro de Oncología de Precisión
🇨🇱Santiago, RM, Chile
CHU Dijon
🇫🇷Dijon Cedex, Bourgogone, France
Centre Eugène Marquis
🇫🇷Rennes, Ille Et Vilaine, France
Institut Bergonié
🇫🇷Bordeaux, France
Centre Léon Bérard
🇫🇷Lyon, France
Istituto Nazionale Tumori IRCCS Fondazione "G Pascale"
🇮🇹Naples, Napoli, Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
🇮🇹Bologna, Italy
Istituto Oncologico Veneto-IOV IRCCS
🇮🇹Padova, Italy
Institut Gustave Roussy
🇫🇷Villejuif, France
Helios Klinikum Berlin-Buch
🇩🇪Berlin, Germany
University Hospital Essen (Universitätsklinikum Essen)
🇩🇪Essen, Germany
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
Università Campus Bio-Medico di Roma
🇮🇹Roma, Italy
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
UMC Groningen
🇳🇱Groningen, Netherlands
LUMC
🇳🇱Leiden, Netherlands
Oslo University Hospital
🇳🇴Oslo, Norway
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Narodowy Instytut Onkologii Im . Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
🇵🇱Warsaw, Warszawa, Poland
Complejo Hospitalario Universitario de Vigo - Hospital Alvaro Cunqueiro
🇪🇸Vigo, Pontevedra, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
The Royal Marsden Hospital NHS Foundation Trust
🇬🇧London, Greater London, United Kingdom
St. James University Hospital
🇬🇧Leeds, West Yorkshire, United Kingdom