Clinical trial NCT05734105: A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib
Official title: An International, Phase 3, Randomized, Multicenter, Open-label Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With KIT Exon 11 and Co-occurring KIT Exons 17 and/or 18 Mutations Who Were Previously Treated With Imatinib
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: GIST
Keywords: advanced gastrointestinal tumors
gastrointestinal stromal tumors
imatinib
ripretinib
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2023-02-17
Enrollment: 54
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 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.


Eligibility criteria: Inclusion Criteria:

1. Male or female ≥18 years of age.
2. Histologic diagnosis of GIST with co-occurring KIT exons 11+17/18 mutations confirmed by ctDNA sample.
3. Participants must have advanced GIST and radiologic progression on imatinib treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2 at screening.
5. Female participants of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug.
6. Participants of reproductive potential must agree to follow contraception requirements.
7. Participants must have at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug.
8. Adequate organ function and bone marrow reserve based on laboratory assessments performed at screening.

Exclusion Criteria:

1. History of KIT exon 9 mutation or detection of KIT exon 9, 13, or 14 mutations in a ctDNA sample.
2. Has known active central nervous system metastases.
3. 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.
4. 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.
5. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug.
6. 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.
7. Gastrointestinal abnormalities including, but not limited to:

   1. inability to take oral medication
   2. malabsorption syndromes
   3. requirement for intravenous alimentation
8. Any active bleeding excluding hemorrhoidal or gum bleeding.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to end of treatment; up to approximately 48 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to end of treatment; up to approximately 48 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 48 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: M Health Fairview University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Northwell Health Cancer Institute/ R.J. Zuckerberg Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Florianópolis
country: Brazil
facility: CEPEN - Centro de Pesquisa e Ensino em Saude de Santa Catarina
state: Santa Catarina
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos - Fundacao Pio XII
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital Sirio-Libanes
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital 9 de Julho
state: SP
city: Rio De Janeiro
country: Brazil
facility: INCA - Instituto Nacional de Cancer
city: São Paulo
country: Brazil
facility: AC Camargo Câncer Center
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Centre
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Las Condes
country: Chile
facility: Clínica San Carlos De Apoquindo Red Salud UC Christus
state: RM
city: Santiago
country: Chile
facility: Centro de Oncología de Precisión
state: RM
city: Dijon Cedex
country: France
facility: CHU Dijon
state: Bourgogone
city: Rennes
country: France
facility: Centre Eugène Marquis
state: Ille Et Vilaine
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lyon
country: France
facility: Centre Léon Bérard
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Essen
country: Germany
facility: University Hospital Essen (Universitätsklinikum Essen)
city: Naples
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione "G Pascale"
state: Napoli
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Padova
country: Italy
facility: Istituto Oncologico Veneto-IOV IRCCS
city: Palermo
country: Italy
facility: U.O.C. Oncologia Medica
city: Roma
country: Italy
facility: Università Campus Bio-Medico di Roma
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Groningen
country: Netherlands
facility: UMC Groningen
city: Leiden
country: Netherlands
facility: LUMC
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii Im . Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
state: Warszawa
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo - Hospital Alvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia - IVO
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital NHS Foundation Trust
state: Greater London
city: Leeds
country: United Kingdom
facility: St. James University Hospital
state: West Yorkshire
Study officials:
affiliation: Deciphera Pharmaceuticals, LLC
name: Clinical Team
role: STUDY_DIRECTOR
References: