(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST
- Registration Number
- NCT03465722
- Lead Sponsor
- Blueprint Medicines Corporation
- Brief Summary
This is an open-label, randomized, Phase 3 study in patients with locally advanced unresectable or metastatic GIST (advanced GIST) of avapritinib (also known as BLU-285) versus regorafenib in patients previously treated with imatinib and 1 or 2 other TKIs.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 476
- Patients who are ≥ 18 years of age.
- Patients who have histologically confirmed metastatic or unresectable GIST.
- Patients who received imatinib and 1 or 2 other TKIs as prior treatment regimens. Patients who experienced intolerance to prior therapies must have objective disease progression prior to enrollment onto BLU-285-1303 study.
- Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.
- Patients who have received prior treatment with avapritinib or regorafenib.
- Patients who have previously received more than 3 different TKI treatment regimens.
- Patients who are known to be both V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor alpha (PDGRFα) wild type.
- Patients who received any systemic anticancer therapy within 1 week before the first dose of study drug.
- Patients who have clinically significant cardiovascular disease
- Patients have experienced arterial thrombotic or embolic events within 6 months before the first dose of study drug, or venous thrombotic events within 14 days of the first dose of study drug
- Patients who have experienced any hemorrhage or bleeding event NCI CTCAE version 5.0 Grade 3 or higher within 4 weeks before the first dose of study drug
- Patients who have a known risk of intracranial bleeding, or a history of intracranial bleeding within 1 year prior to the first dose of study drug
- Patients who have a symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.
- Patients who have poor organ function as defined by laboratory parameters specified in the protocol.
- Patients who have received neutrophil growth factor support within 14 days of first dose of study drug.
- Patients who require therapy with a concomitant medication that is a strong inhibitor or strong inducer of CYP3A4.
- Patients who have had a major surgical procedure within 14 days of the first dose of study drug. Patient has significant traumatic injury within 28 days before the first dose of study drug.
- Patients who have a history of another primary malignancy that has been diagnosed or required therapy within 3 years before first dose of study drug.
- Patients who have a history of a seizure disorder requiring anti-seizure medication.
- Patients who have metastases to the brain.
- Patients who have a QT interval corrected using Fridericia's formula (QTcF) of > 450 msec.
- Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of the first dose of study drug and for at least 60 days after the last dose of study drug. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of the first dose of study drug and for at least 90 days after the last dose of study drug.
- Women who are pregnant.
- Women who are breastfeeding.
- Patients who have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality as determined by the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description avapritinib avapritinib 300 mg PO QD regorafenib regorafenib 160 mg PO QD
- Primary Outcome Measures
Name Time Method Efficacy of Avapritinib Based on Progression-free Survival (PFS) Determined by Central Radiological Assessment Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST), Version 1.1 24 Months To demonstrate the efficacy of avapritinib based on progression-free survival (PFS) determined by central radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST following 2 or 3 regimens of prior treatment with a tyrosine kinase inhibitor (TKI), including imatinib, compared to patients treated with regorafenib. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 24 Months To evaluate objective response rate (ORR) determined by central radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. A complete response (CR) per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response (PR) is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR
Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib 24 Months To evaluate overall survival (OS) in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib
European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30). Change in Individual Scores in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib Difference between baseline and week 12 of treatment The Global Health Status Score is derived from question 29 and 30 on the EORTC-QLQ-C30 tool. The change in score was assessed between baseline and week 12 in patients treated with advanced GIST treated with avapritinib compared to patients treated with regorafenib. The Global Health Status Score score range is 0 to 100 with a higher score indicating better global health status. A positive change indicates improvement in global health status.
Trial Locations
- Locations (112)
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Northwestern Medicine
🇺🇸Chicago, Illinois, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The Canberra Hospital
🇦🇺Garran, Australia
Jewish General Hospital
🇨🇦Montréal, Canada
Medical Oncology University Debrecen
🇭🇺Debrecen, Hungary
Rocky Mountain Cancer Centers
🇺🇸Boulder, Colorado, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Leuven Cancer Institute
🇧🇪Leuven, Belgium
University of Pécs
🇭🇺Pécs, Hungary
Onkologická klinika Fakultní nemocnice Olomouc
🇨🇿Olomouc, Czechia
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Fackultni Nemocnice v Motole
🇨🇿Praha, Czechia
AOUC Azienda Ospedaliero - Universitaria Careggi
🇮🇹Firenze, Italy
Summit Cancer Centers
🇺🇸Spokane, Washington, United States
Fovarosi Onkormanyzat Szent Laszlo Korhaz
🇭🇺Budapest, Hungary
Rupercht-Karls-Universitaet Heidelberg
🇩🇪Mannheim, Germany
Magyar Honvédség Egészségügyi Központ Onkológiai Osztály
🇭🇺Budapest, Hungary
Campus Bio-Medico - Oncology Medica
🇮🇹Roma, Italy
Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Institut Català d'Oncologia - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z W-MCO
🇵🇱Olsztyn, Poland
Universita degli Studi di Palermo - Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Ajou University Hospital
🇰🇷Suwon-si, Gyeong Gi-do, Korea, Republic of
Vall d'Hebron
🇪🇸Barcelona, Spain
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Sanodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie, Oddzial Kliniczny Onkologii
🇵🇱Kraków, Poland
Maria Skodowska Curie Memorial Cancer Centre and Institute of Oncology
🇵🇱Warszawa, Poland
Skanes University Hospital
🇸🇪Lund, Sweden
Azienda Ospedaliero Universitaria Sant'Orsola Malpighi
🇮🇹Bologna, Italy
Hospital La Paz
🇪🇸Madrid, Spain
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Studienzentrale GbR Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt
🇩🇪Lubeck, Germany
Hospital Virgen del Rocio
🇪🇸Sevilla, Spain
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Dolnoslaskie Centrum Onkologii we Wrocawiu
🇵🇱Wrocław, Poland
Hospital Universitario Gregorio Marañón
🇪🇸Madrid, Spain
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Chinese PLA General Hospital
🇨🇳Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, China
The First Affiliated Hospital of Sun Yat-sen University
🇨🇳Guangzhou, China
The Sixth Affiliated Hospital of Sun Yat-Sen University
🇨🇳Guangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Shanghai Jiaotong University School of Medicine, Renji Hospital
🇨🇳Shanghai, China
Candiolo Cancer Institute - FPO, IRCCS
🇮🇹Candiolo, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
🇮🇹Milano, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
UNICANCER - Lyon, Centre Léon-Bérard
🇫🇷Lyon, France
Institute Paoli Calmettes
🇫🇷Marseille, France
La Timone University Hospital
🇫🇷Marseille, France
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Fundacion Instituto Valenciano de Oncologia, Servicio de Oncologia
🇪🇸Valencia, Spain
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Medical College of Wisconsin - Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
University of Miami
🇺🇸Miami, Florida, United States
OHSU - Knight Cancer Institute
🇺🇸Portland, Oregon, United States
Monash Health
🇦🇺Clayton, Australia
University of Texas MD Anderson
🇺🇸Houston, Texas, United States
Texas Oncology - Waco
🇺🇸Waco, Texas, United States
UCLA Hematology/Oncology - Santa Monica
🇺🇸Santa Monica, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Washington Hospital Center - Oncology and Hematology
🇺🇸Washington, District of Columbia, United States
Institut Bergonié
🇫🇷Bordeaux, France
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Washington University in Saint Louis
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
USO - Texas Oncology
🇺🇸Dallas, Texas, United States
Flinders Medical Center
🇦🇺Adelaide, Australia
AKH, Klinik f. Innere Med. I, Onkologie
🇦🇹Wien, Austria
Institut Jules Bordet
🇧🇪Brussels, Belgium
University Health Network
🇨🇦Toronto, Ontario, Canada
West China Hospital Sichuan University
🇨🇳Chengdu, China
The First Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College
🇨🇳Nanning, China
The First Affiliated Hospital of Nanchang Medical University
🇨🇳Nanchang, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, China
Fudan University Zhongshan Hospital
🇨🇳Shanghai, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Affiliated Cancer Hospital of Xinjiang Medical University
🇨🇳Ürümqi, China
Centre Oscar Lambret
🇫🇷Lille, France
HELIOS Klinikum Bad Saarow
🇩🇪Bad Saarow, Germany
Institut Curie
🇫🇷Paris, France
HELIOS Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Medizinische Fakultät Carl Gustav Carus
🇩🇪Dresden, Germany
Universitaetsklindum Essen
🇩🇪Essen, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Germany
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Radboud University Medical Center
🇳🇱Nijmegen, Netherlands
The Royal Marsden Hospital
🇬🇧London, United Kingdom
Texas Oncology - Denton South
🇺🇸Denton, Texas, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Centre Rene Gauducheau
🇫🇷Saint-Herblain, France
Gustave Roussy Cancer Campus
🇫🇷Villejuif, France
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
Guy's Hospital
🇬🇧London, United Kingdom