A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib
- Conditions
- Gastrointestinal Stromal Tumors
- Interventions
- Registration Number
- NCT03673501
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
This is a 2-arm, randomized, open-label, international, multicenter study comparing the efficacy of ripretinib to sunitinib in GIST patients who progressed on or were intolerant to first-line anticancer treatment with imatinib. Approximately 426 patients will be randomized in a 1:1 ratio to ripretinib 150 mg once daily (continuous dosing for 6 week cycles) or sunitinib 50 mg once daily (6 week cycles, 4 weeks on, 2 weeks off).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 453
- Patients ≥ 18 years of age at the time of informed consent.
- Histologic diagnosis of GIST and must be able to provide an archival tumor tissue sample, otherwise, a fresh biopsy is required.
- Molecular pathology report must be available. If molecular pathology report is not available or insufficient, an archival tumor tissue sample or fresh biopsy is required for mutation status confirmation by the central laboratory prior to randomization.
- Patients must have progressed on imatinib or have documented intolerance to imatinib.
- Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of ≤ 2 at screening.
- Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening and negative pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug.
- Patients of reproductive potential must agree to follow the contraception requirements outlined in the study protocol.
- Patients must have at least 1 measurable lesion according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1 (non nodal lesions must be ≥ 1.0 cm in the long axis or ≥ double the slice thickness in the long axis) within 21 days prior to the first dose of study drug.
- Adequate organ function and bone marrow reserve as indicated by the central laboratory assessments performed at screening.
- Resolution of all toxicities from prior therapy to ≤ Grade 1 (or patient baseline) within 1 week prior to the first dose of study drug (excluding alopecia and ≤ Grade 3 clinically asymptomatic lipase, amylase, and creatine phosphokinase laboratory abnormalities).
- The patient is capable of understanding and complying with the protocol and the patient has signed the informed consent document. Signed informed consent form (ICF) must be obtained before any study-specific procedures are performed and the patient must agree to not participate in any other interventional clinical trial while on treatment in this clinical trial. Participation in a noninterventional study (including observational studies) is permitted.
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Treatment with any other line of therapy in addition to imatinib for advanced GIST. Imatinib-containing combination therapy in the first-line setting is not allowed.
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Patients with a prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible.
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Patient 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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Left ventricular ejection fraction (LVEF) < 50% at screening.
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Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
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Venous thrombotic events (e.g. deep vein thrombosis) or pulmonary arterial events (e.g. pulmonary embolism) within 1 month before the first dose of study drug. Patients on stable anticoagulation therapy for at least one month are eligible.
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12-lead ECG demonstrating QT interval corrected (QTc) by Fridericia's formula > 450 ms in males or > 470 ms in females at screening or history of long QTc syndrome
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Use of known substrates or inhibitors of breast cancer resistance protein (BCRP) transporters within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug.
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Major surgeries (e.g. abdominal laparotomy) within 4 weeks of the first dose of study drug. All major surgical wounds must be healed and free of infection or dehiscence before the first dose of study drug.
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Any other clinically significant comorbidities.
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Known human immunodeficiency virus or hepatitis C infection only if the patient is taking medications that are excluded per protocol, active hepatitis B, or active hepatitis C infection.
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If female, the patient is pregnant or lactating.
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Known allergy or hypersensitivity to any component of the study drug.
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Gastrointestinal abnormalities including but not limited to:
- inability to take oral medication
- malabsorption syndromes
- requirement for intravenous (IV) 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 Ripretinib Ripretinib Ripretinib (150 mg) once a day continuous dosing for 6-week (42 days) cycles Sunitinib Sunitinib Sunitinib (50 mg) once a day in 6-week (42 days) cycles with 4 weeks continuous dosing followed by 2 week break.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) in the All Patient (AP) Intent to Treat (ITT) Population From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years) PFS is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the independent radiologic review using modified RECIST Version 1.1-(mRECIST 1.1) Gastrointestinal stromal tumor (GIST) specific, or death due to any cause. Per mRECIST 1.1, progression was defined using mRECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Progression Free Survival (PFS) in the KIT Exon 11 Intent to Treat (ITT) Population From date of randomization to earliest documented evidence of disease progression, or death due to any cause (up to 2.1 years) PFS is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the independent radiologic review using modified RECIST Version 1.1-(mRECIST 1.1) GIST specific, or death due to any cause. Per mRECIST 1.1, progression was defined using mRECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) in the KIT Exon 11 Intent to Treat (ITT) Population From date of randomization until death due to any cause (up to 3.33 years) OS was defined as the time from the date of randomization until death due to any cause.
Overall Survival (OS) in the All Patient (AP) Intent to Treat (ITT) Population From date of randomization until death due to any cause (up to 3.33 years) OS was defined as the time from the date of randomization until death due to any cause.
Objective Response Rate (ORR) in the KIT Exon 11 Intent to Treat (ITT) Population Population From confirmed CR or PR to disease progression (up to 1.74 years) ORR was defined as the proportion of patients with confirmed complete response (CR) + confirmed partial response (PR) based on independent radiologic review using modified RECIST (mRECIST) criteria as best overall response. Per mRECIST 1.1 criteria, complete response is defined as disappearance of all target lesions; partial response is defined as \>=30% decrease in the sum of the longest diameter of target lesions.
Objective Response Rate (ORR) in the All Patient (AP) Intent to Treat (ITT) Population From confirmed CR or PR to disease progression (up to 1.74 years) ORR was defined as the proportion of patients with confirmed complete response (CR) + confirmed partial response (PR) based on independent radiologic review using modified RECIST (mRECIST) criteria as best overall response. Per mRECIST 1.1 criteria, complete response is defined as disappearance of all target lesions; partial response is defined as \>=30% decrease in the sum of the longest diameter of target lesions.
Trial Locations
- Locations (120)
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
UCLA Hematology Oncology Center - Main Site
🇺🇸Los Angeles, California, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Miami Cancer Institute at Baptist Health, Inc.
🇺🇸Miami, Florida, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
IU Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
University of California San Diego Medical Center
🇺🇸La Jolla, California, United States
Washington University School of Medicine - Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Washington Cancer Institute at MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Border Medical Oncology Research Unit
🇦🇺Albury, New South Wales, Australia
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Hopital Maisonneuve-Rosemont
🇨🇦Québec, Canada
Institut Bergonnié
🇫🇷Bordeaux, France
Centre Georges François Leclerc
🇫🇷Dijon, France
IPC
🇫🇷Marseille, France
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital de Basurto
🇪🇸Bilbao, Spain
Università Campus Bio-Medico di Roma
🇮🇹Rome, Italy
Ajou University Hospital
🇰🇷Suwon, Korea, Republic of
Centre Hospitalier Universitaire Vaudois, Fondation du Centre Pluridisciplinaire d'Oncologi
🇨🇭Lausanne, Switzerland
Hospital Universitario HM Madrid Sanchinarro
🇪🇸Madrid, Spain
Instituto Valenciano de Oncología,
🇪🇸Valencia, Spain
Karolinska universitetssjukhuset
🇸🇪Solna, Sweden
Complejo Hospitalario Universitario de Vigo
🇪🇸Vigo, Spain
University College London Hospitals
🇬🇧London, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Stanford Medicine
🇺🇸Stanford, California, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
The Monter Cancer Center
🇺🇸Lake Success, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Georgia Cancer Specialists
🇺🇸Sandy Springs, Georgia, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Princess Alexandara Hospital
🇦🇺Woolloongabba, Australia
Fakultni nemocnice v Motole
🇨🇿Prague, Czechia
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Hopital La Timone
🇫🇷Marseille, France
ICO - Site René Gauducheau
🇫🇷Saint Herblain, France
HELIOS Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Debreceni Egyetem
🇭🇺Debrecen, Hungary
Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
The Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
Leiden University Medical Centre
🇳🇱Leiden, Netherlands
Royal Marsden Hospital - Fulham
🇬🇧London, United Kingdom
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
University of Colorado Hospital - Anschutz Cancer Pavillion
🇺🇸Aurora, Colorado, United States
Smilow Cancer Hospital at Yale
🇺🇸New Haven, Connecticut, United States
Orlando Health UF Health Cancer Center
🇺🇸Orlando, Florida, United States
Norton Cancer Institute, Audubon Hospital Campus
🇺🇸Louisville, Kentucky, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Minnesota Medical Center-Fairview
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University Center for Health and Healing
🇺🇸Portland, Oregon, United States
Froedtert Hospital-Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Rabin Medical Cente
🇮🇱Petah Tikva, Israel
Universita degli Studi di Palermo
🇮🇹Palermo, Italy
Universitaetsspital Zuerich, Klinik fuer Onkologie
🇨🇭Zurich, Switzerland
China Medical University Hospital
🇨🇳Taichung, Taiwan
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Sanatorio Allende
🇦🇷Córdoba, Cordoba, Argentina
Clinica San Carlos de Apoquindo Red Salud UC Christs
🇨🇱Santiago, Chile
CHU Poitiers-Hopital la Miletrie
🇫🇷Poitiers, France
Technische Universitat Dresden
🇩🇪Dresden, Germany
Centre Léon Bérard
🇫🇷Lyon, France
Centre Oscar Lambret
🇫🇷Lille Cedex, France
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
🇮🇹Bologna, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
Chang Gung Memorial Hospital
🇨🇳Linkou, Taoyuan County, Taiwan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Ashford Cancer Centre Research
🇦🇺Kurralta Park, South Australia, Australia
IGR
🇫🇷Paris, France
Magyar Honvedseg Egeszsegugyi Kozpont
🇭🇺Budapest, Hungary
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Shamir Medical Center (Assaf Harofeh)
🇮🇱Be'er Ya'akov, Israel
University Medical Center Groningen
🇳🇱Groningen, Netherlands
National Cancer Centre
🇸🇬Singapore, Singapore
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Rutgers Cancer Institute
🇺🇸New Brunswick, New Jersey, United States
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Tel-Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
🇵🇱Warsaw, Poland
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Instituto Medicao Especializado Alexander Fleming
🇦🇷Buenos Aires, Argentina
West German Cancer Center
🇩🇪Essen, Germany
stituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
🇮🇹Meldola, Italy
IOV - Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Italy
Oslo University Hospital
🇳🇴Oslo, Norway
Kaohsiung Chang Gung Memorial Hospital,
🇨🇳Kaohsiung, Taiwan
National Chen Kung University Hospital
🇨🇳Tainan, Taiwan
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Montefiore Medical Center-Montefiore Medical Park
🇺🇸Bronx, New York, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States