Clinical trial NCT03465722: (VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST
Official title: An International, Multicenter, Open-label, Randomized, Phase 3 Study of BLU-285 vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic Gastrointestinal Stromal Tumor (GIST)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: GIST
Keywords: Other Relapsed or Refractory Solid Tumors
BLU-285
BLU 285
BLUE-285
BLUE 285
Avapritinib
GIST imatinib relapse
GIST gleevec relapse
GIST KIT
GIST relapse
GIST refractory
GIST imatinib intolerance
GIST TKI treatment
GIST tyrosine kinase inhibitor treatment
GIST TKI
GIST tyrosine kinase inhibitor
Advanced GIST
GIST mutations
GIST treatments
Blueprint GIST
Relapsed GIST clinical trial
Refractory GIST clinical trial
KIT-mutant GIST
cancer gist
gastrointestinal stromal tumor
gist cancer
PDGFRA
Lead sponsor: Blueprint Medicines Corporation
Sponsor class: INDUSTRY
First posted: 2018-03-14
Enrollment: 476
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Patients who are ≥ 18 years of age.
2. Patients who have histologically confirmed metastatic or unresectable GIST.
3. 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.
4. Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.

Exclusion Criteria:

1. Patients who have received prior treatment with avapritinib or regorafenib.
2. Patients who have previously received more than 3 different TKI treatment regimens.
3. 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.
4. Patients who received any systemic anticancer therapy within 1 week before the first dose of study drug.
5. Patients who have clinically significant cardiovascular disease
6. 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
7. 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
8. 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
9. Patients who have a symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.
10. Patients who have poor organ function as defined by laboratory parameters specified in the protocol.
11. Patients who have received neutrophil growth factor support within 14 days of first dose of study drug.
12. Patients who require therapy with a concomitant medication that is a strong inhibitor or strong inducer of CYP3A4.
13. 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.
14. 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.
15. Patients who have a history of a seizure disorder requiring anti-seizure medication.
16. Patients who have metastases to the brain.
17. Patients who have a QT interval corrected using Fridericia's formula (QTcF) of \> 450 msec.
18. 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.
19. Women who are pregnant.
20. Women who are breastfeeding.
21. Patients who have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality as determined by the investigator.

Primary outcomes:
measure: 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
timeFrame: 24 Months
Secondary outcomes:
measure: Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1
timeFrame: 24 Months
measure: Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib
timeFrame: 24 Months
measure: 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
timeFrame: Difference between baseline and week 12 of treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center - Oncology and Hematology
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in Saint Louis
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: OHSU - Knight Cancer Institute
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: USO - Texas Oncology
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Denton South
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson
state: Texas
city: Waco
country: United States
facility: Texas Oncology - Waco
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Spokane
country: United States
facility: Summit Cancer Centers
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Froedtert Hospital
state: Wisconsin
city: Adelaide
country: Australia
facility: Flinders Medical Center
city: Clayton
country: Australia
facility: Monash Health
city: Garran
country: Australia
facility: The Canberra Hospital
city: Wien
country: Austria
facility: AKH, Klinik f. Innere Med. I, Onkologie
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: Leuven Cancer Institute
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Chengdu
country: China
facility: West China Hospital Sichuan University
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-Sen University
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang Medical University
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Fudan University Zhongshan Hospital
city: Shanghai
country: China
facility: Shanghai Jiaotong University School of Medicine, Renji Hospital
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Ürümqi
country: China
facility: Affiliated Cancer Hospital of Xinjiang Medical University
city: Olomouc
country: Czechia
facility: Onkologická klinika Fakultní nemocnice Olomouc
city: Praha
country: Czechia
facility: Fackultni Nemocnice v Motole
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: UNICANCER - Lyon, Centre Léon-Bérard
city: Marseille
country: France
facility: Institute Paoli Calmettes
city: Marseille
country: France
facility: La Timone University Hospital
city: Paris
country: France
facility: Institut Curie
city: Saint-Herblain
country: France
facility: Centre Rene Gauducheau
city: Villejuif
country: France
facility: Gustave Roussy Cancer Campus
city: Bad Saarow
country: Germany
facility: HELIOS Klinikum Bad Saarow
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Dresden
country: Germany
facility: Medizinische Fakultät Carl Gustav Carus
city: Essen
country: Germany
facility: Universitaetsklindum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Lubeck
country: Germany
facility: Studienzentrale GbR Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt
city: Mannheim
country: Germany
facility: Rupercht-Karls-Universitaet Heidelberg
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Szent Laszlo Korhaz
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ Onkológiai Osztály
city: Debrecen
country: Hungary
facility: Medical Oncology University Debrecen
city: Pécs
country: Hungary
facility: University of Pécs
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Sant'Orsola Malpighi
city: Candiolo
country: Italy
facility: Candiolo Cancer Institute - FPO, IRCCS
city: Firenze
country: Italy
facility: AOUC Azienda Ospedaliero - Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori Milano
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Palermo
country: Italy
facility: Universita degli Studi di Palermo - Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Campus Bio-Medico - Oncology Medica
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeong Gi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Kraków
country: Poland
facility: Sanodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie, Oddzial Kliniczny Onkologii
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z W-MCO
city: Warszawa
country: Poland
facility: Maria Skodowska Curie Memorial Cancer Centre and Institute of Oncology
city: Wrocław
country: Poland
facility: Dolnoslaskie Centrum Onkologii we Wrocawiu
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals
city: Barcelona
country: Spain
facility: Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia, Servicio de Oncologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Lund
country: Sweden
facility: Skanes University Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
References:
citation: Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schoffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol. 2021 Oct 1;39(28):3128-3139. doi: 10.1200/JCO.21.00217. Epub 2021 Aug 3.
citation: Gebreyohannes YK, Wozniak A, Zhai ME, Wellens J, Cornillie J, Vanleeuw U, Evans E, Gardino AK, Lengauer C, Debiec-Rychter M, Sciot R, Schoffski P. Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Jan 15;25(2):609-618. doi: 10.1158/1078-0432.CCR-18-1858. Epub 2018 Oct 1.