A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib

GIST Clinical Trial

— INSIGHT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05734105
• Other study ID #: DCC-2618-03-003
• Status: Recruiting
• Phase: Phase 3
• Start date: December 13, 2023
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Deciphera Pharmaceuticals LLC
• Contact: Clinical Team
• Phone: 785-830-2100
• Email: Clinicaltrials[@]deciphera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: December 2027
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

9. Resolution of all toxicities from prior therapy to Grade =1 (or participant baseline) within 1 week prior to the first dose of study drug.

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.

Related Conditions & MeSH terms

• GIST

Intervention

Drug:
• Ripretinib
50 mg tablets
• Sunitinib
12.5 mg tablets

Locations

Country	Name	City	State
Australia	Alfred Health	Melbourne	Victoria
Brazil	Hospital de Cancer de Barretos - Fundacao Pio XII	Barretos	Sao Paulo
Brazil	CEPEN - Centro de Pesquisa e Ensino em Saude de Santa Catarina	Florianópolis	Santa Catarina
Brazil	INCA - Instituto Nacional de Cancer	Rio De Janeiro
Brazil	AC Camargo Câncer Center	São Paulo
Brazil	Hospital 9 de Julho	São Paulo	SP
Brazil	Hospital Sirio-Libanes	São Paulo	Sao Paulo
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	McGill University Health Centre	Montréal	Quebec
Canada	University Health Network, Princess Margaret Cancer Centre	Toronto	Ontario
Chile	Clínica San Carlos De Apoquindo Red Salud UC Christus	Las Condes	RM
France	Centre Léon Bérard	Lyon
France	Institut Gustave Roussy	Villejuif
Germany	Helios Klinikum Berlin-Buch	Berlin
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milan
Italy	Istituto Nazionale Tumori IRCCS Fondazione "G Pascale"	Naples	Napoli
Italy	Istituto Oncologico Veneto-IOV IRCCS	Padova
Italy	U.O.C. Oncologia Medica	Palermo
Italy	Università Campus Bio-Medico di Roma	Roma
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Netherlands	UMC Groningen	Groningen
Netherlands	LUMC	Leiden
Poland	Narodowy Instytut Onkologii Im . Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warsaw	Warszawa
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Instituto Valenciano de Oncologia - IVO	Valencia
Spain	Complejo Hospitalario Universitario de Vigo - Hospital Alvaro Cunqueiro	Vigo	Pontevedra
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	St. James University Hospital	Leeds	West Yorkshire
United Kingdom	The Royal Marsden Hospital NHS Foundation Trust	London	Greater London
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Boston Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
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	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	M Health Fairview University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Yale University	New Haven	Connecticut
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	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Fred Hutchinson Cancer Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Deciphera Pharmaceuticals LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Chile,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	The time from randomization until documented progressive disease (PD) based on IRR per mRECIST or death due to any cause, whichever occurs first.	Up to end of treatment; up to approximately 48 months
Secondary	Objective Response Rate (ORR)	Compare ORR by IRR of ripretinib vs sunitinib using mRECIST	Up to end of treatment; up to approximately 48 months
Secondary	Overall Survival (OS)	Compare OS of ripretinib vs sunitinib	Up to approximately 48 months