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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05734105




Registration number
NCT05734105
Ethics application status
Date submitted
8/02/2023
Date registered
17/02/2023
Date last updated
28/06/2024

Titles & IDs
Public title
A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib
Scientific 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
Secondary ID [1] 0 0
DCC-2618-03-003
Universal Trial Number (UTN)
Trial acronym
INSIGHT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
GIST 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ripretinib
Treatment: Drugs - Sunitinib

Experimental: Ripretinib - 150 mg QD of ripretinib (3×50 mg tablets) will be dosed continuously in repeated 42-day cycles.

Active comparator: 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.


Treatment: Drugs: Ripretinib
50 mg tablets

Treatment: Drugs: Sunitinib
12.5 mg tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Up to end of treatment; up to approximately 48 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to end of treatment; up to approximately 48 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 48 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
54
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Health - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
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United States of America
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Florida
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Minnesota
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United States of America
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New York
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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Oregon
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United States of America
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Texas
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United States of America
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Washington
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Brazil
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Santa Catarina
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Brazil
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Sao Paulo
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Brazil
State/province [15] 0 0
SP
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Brazil
State/province [16] 0 0
Rio De Janeiro
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Brazil
State/province [17] 0 0
São Paulo
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Canada
State/province [18] 0 0
Ontario
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Canada
State/province [19] 0 0
Quebec
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Chile
State/province [20] 0 0
RM
Country [21] 0 0
France
State/province [21] 0 0
Lyon
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France
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Villejuif
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Germany
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Berlin
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Italy
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Napoli
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Italy
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Bologna
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Italy
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Milan
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Italy
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Padova
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Italy
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Palermo
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Italy
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Roma
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Korea, Republic of
State/province [30] 0 0
Seoul
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Netherlands
State/province [31] 0 0
Groningen
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Netherlands
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Leiden
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Poland
State/province [33] 0 0
Warszawa
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Spain
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Pontevedra
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Spain
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Barcelona
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Spain
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Valencia
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Taiwan
State/province [37] 0 0
Taichung
Country [38] 0 0
Taiwan
State/province [38] 0 0
Taipei
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United Kingdom
State/province [39] 0 0
Greater London
Country [40] 0 0
United Kingdom
State/province [40] 0 0
West Yorkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Deciphera Pharmaceuticals LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05734105
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Team
Address 0 0
Deciphera Pharmaceuticals LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Team
Address 0 0
Country 0 0
Phone 0 0
785-830-2100
Fax 0 0
Email 0 0
Clinicaltrials@deciphera.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05734105