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

April 24, 2024 updated by: Deciphera Pharmaceuticals LLC

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • Alfred Health
  • Brazil
      • Rio De Janeiro, Brazil, 20231
        • Recruiting
        • INCA - Instituto Nacional de Cancer
      • São Paulo, Brazil, 01509-900
        • Recruiting
        • AC Camargo Câncer Center
    • SP
      • São Paulo, SP, Brazil, 01409-002
        • Recruiting
        • Hospital 9 de Julho
    • Santa Catarina
      • Florianópolis, Santa Catarina, Brazil, 88034-000
        • Recruiting
        • CEPEN - Centro de Pesquisa e Ensino em Saude de Santa Catarina
    • Sao Paulo
      • Barretos, Sao Paulo, Brazil, 14748-400
        • Recruiting
        • Hospital de Cancer de Barretos - Fundacao Pio XII
      • São Paulo, Sao Paulo, Brazil, 01308
        • Recruiting
        • Hospital Sirio-Libanes
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Recruiting
        • Juravinski Cancer Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • University Health Network, Princess Margaret Cancer Centre
    • Quebec
      • Montréal, Quebec, Canada, H4A 3J1
        • Recruiting
        • McGill University Health Centre
  • Chile
    • RM
      • Las Condes, RM, Chile, 7620002
        • Recruiting
        • Clínica San Carlos De Apoquindo Red Salud UC Christus
  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
      • Palermo, Italy, 90127
        • Recruiting
        • U.O.C. Oncologia Medica
      • Roma, Italy, 00128
        • Recruiting
        • Università Campus Bio-Medico di Roma
    • Napoli
      • Naples, Napoli, Italy, 80131
        • Recruiting
        • Istituto Nazionale Tumori IRCCS Fondazione "G Pascale"
  • Korea, Republic of
      • Seoul, Korea, Republic of, 05505
        • Recruiting
        • Asan Medical Center
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center
  • Netherlands
      • Groningen, Netherlands, 9713
        • Recruiting
        • UMC Groningen
      • Leiden, Netherlands, 2333 ZA
        • Recruiting
        • LUMC
  • Poland
    • Warszawa
      • Warsaw, Warszawa, Poland, 02-781
        • Recruiting
        • Narodowy Instytut Onkologii Im . Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitario Vall d'Hebron
      • Barcelona, Spain, 08041
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau
      • Valencia, Spain, 46009
        • Recruiting
        • Instituto Valenciano de Oncologia - IVO
    • Pontevedra
      • Vigo, Pontevedra, Spain, 36312
        • Recruiting
        • Complejo Hospitalario Universitario de Vigo - Hospital Alvaro Cunqueiro
  • Taiwan
      • Taichung, Taiwan, 40447
        • Recruiting
        • China Medical University Hospital
      • Taipei, Taiwan, 11217
        • Recruiting
        • Taipei Veterans General Hospital
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, SW3 6JJ
        • Recruiting
        • The Royal Marsden Hospital NHS Foundation Trust
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS9 7TF
        • Recruiting
        • St. James University Hospital
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • M Health Fairview University of Minnesota Medical Center
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 11042
        • Recruiting
        • Northwell Health Cancer Institute/ R.J. Zuckerberg Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • OU Health Stephenson Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ripretinib
150 mg QD of ripretinib (3×50 mg tablets) will be dosed continuously in repeated 42-day cycles.
Drug: Ripretinib
50 mg tablets
Other Names:
  • QINLOCK, DCC-2618
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.
Drug: Sunitinib
12.5 mg tablets
Other Names:
  • Sutent

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: 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.
Up to end of treatment; up to approximately 48 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to end of treatment; up to approximately 48 months
Compare ORR by IRR of ripretinib vs sunitinib using mRECIST
Up to end of treatment; up to approximately 48 months
Overall Survival (OS)
Time Frame: Up to approximately 48 months
Compare OS of ripretinib vs sunitinib
Up to approximately 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Deciphera Pharmaceuticals LLC

Investigators

  • Study Director: Clinical Team, Deciphera Pharmaceuticals LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 13, 2023

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

February 8, 2023

First Submitted That Met QC Criteria

February 8, 2023

First Posted (Actual)

February 17, 2023

Study Record Updates

Last Update Posted (Actual)

April 25, 2024

Last Update Submitted That Met QC Criteria

April 24, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DCC-2618-03-003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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