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GISTPhase 3NCT03465722

(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST

A Phase 3 study testing avapritinib and regorafenib in people with GIST, run by Blueprint Medicines Corporation at 114 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
GIST
What is being tested?
avapritinib and regorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
476 participants
Where
114 sitesin 18 countries
Study dates
26 Mar 2018to 15 Sep 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 21Show fewer
  • 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.

Trial locations and contacts

114 sites in 18 countries.

114 sites in 18 countries

United States30 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Northside Hospital

    Atlanta, Georgia, 30341

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Rocky Mountain Cancer Centers

    Boulder, Colorado, 80303

  • Northwestern Medicine

    Chicago, Illinois, 60611

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Ohio State University

    Columbus, Ohio, 43210

  • USO - Texas Oncology

    Dallas, Texas, 75246

  • Texas Oncology - Denton South

    Denton, Texas, 76210

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Texas MD Anderson

    Houston, Texas, 77030

  • Mayo Clinic Cancer Center

    Jacksonville, Florida, 32224

  • University of Miami

    Miami, Florida, 33146

  • Medical College of Wisconsin - Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic Cancer Center

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • OHSU - Knight Cancer Institute

    Portland, Oregon, 97239

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • UCLA Hematology/Oncology - Santa Monica

    Santa Monica, California, 90404

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Summit Cancer Centers

    Spokane, Washington, 99216

  • Washington University in Saint Louis

    St Louis, Missouri, 63130

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Texas Oncology - Waco

    Waco, Texas, 76712

  • Washington Hospital Center - Oncology and Hematology

    Washington D.C., District of Columbia, 20010

Other trials in United States

China19 sites

  • Beijing Cancer Hospital

    Beijing

  • Chinese PLA General Hospital

    Beijing

  • West China Hospital Sichuan University

    Chengdu

  • The First Affiliated Hospital of Chongqing Medical University

    Chongqing

  • Fujian Medical University Union Hospital

    Fuzhou

  • The First Affiliated Hospital of Sun Yat-sen University

    Guangzhou

  • The Sixth Affiliated Hospital of Sun Yat-Sen University

    Guangzhou

  • The First Affiliated Hospital, Zhejiang University

    Hangzhou

  • Harbin Medical University Cancer Hospital

    Harbin

  • The First Affiliated Hospital of Nanchang Medical University

    Nanchang

  • Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College

    Nanning

  • The Affiliated Hospital of Qingdao University

    Qingdao

  • Fudan University Shanghai Cancer Center

    Shanghai

  • Fudan University Zhongshan Hospital

    Shanghai

  • Shanghai Jiaotong University School of Medicine, Renji Hospital

    Shanghai

  • Liaoning Cancer Hospital & Institute

    Shenyang

  • Tianjin Cancer Hospital

    Tianjin

  • Affiliated Cancer Hospital of Xinjiang Medical University

    Ürümqi

  • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

    Wuhan

Other trials in China

Spain9 sites

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • Institut Català d'Oncologia - Hospital Duran i Reynals

    Barcelona

  • Vall d'Hebron

    Barcelona

  • Hospital La Paz

    Madrid

  • Hospital Universitario Gregorio Marañón

    Madrid

  • Hospital Universitario Puerta de Hierro

    Madrid

  • Hospital Virgen del Rocio

    Seville

  • Fundacion Instituto Valenciano de Oncologia, Servicio de Oncologia

    Valencia

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

France8 sites

  • Institut Bergonié

    Bordeaux

  • Centre Oscar Lambret

    Lille

  • UNICANCER - Lyon, Centre Léon-Bérard

    Lyon, 69008

  • Institute Paoli Calmettes

    Marseille

  • La Timone University Hospital

    Marseille

  • Institut Curie

    Paris

  • Centre Rene Gauducheau

    Saint-Herblain

  • Gustave Roussy Cancer Campus

    Villejuif

Other trials in France

Germany7 sites

  • HELIOS Klinikum Bad Saarow

    Bad Saarow

  • HELIOS Klinikum Berlin-Buch

    Berlin

  • Medizinische Fakultät Carl Gustav Carus

    Dresden

  • Universitaetsklindum Essen

    Essen

  • Universitätsklinikum Frankfurt

    Frankfurt

  • Studienzentrale GbR Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt

    Lübeck

  • Rupercht-Karls-Universitaet Heidelberg

    Mannheim

Other trials in Germany

Italy7 sites

  • Azienda Ospedaliero Universitaria Sant'Orsola Malpighi

    Bologna

  • Candiolo Cancer Institute - FPO, IRCCS

    Candiolo

  • AOUC Azienda Ospedaliero - Universitaria Careggi

    Florence

  • Fondazione IRCCS Istituto Nazionale dei Tumori Milano

    Milan

  • Istituto Europeo di Oncologia

    Milan

  • Universita degli Studi di Palermo - Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

    Palermo

  • Campus Bio-Medico - Oncology Medica

    Roma

Other trials in Italy

South Korea5 sites

  • Asan Medical Center

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Severance Hospital

    Seoul

  • Ajou University Hospital

    Suwon, Gyeong Gi-do

Other trials in South Korea

United Kingdom5 sites

  • Beatson West of Scotland Cancer Centre

    Glasgow

  • The Royal Marsden Hospital

    London, SW3 6JJ

  • Guy's Hospital

    London

  • The Christie NHS Foundation Trust

    Manchester

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield

Other trials in United Kingdom

Hungary4 sites

  • Fovarosi Onkormanyzat Szent Laszlo Korhaz

    Budapest

  • Magyar Honvédség Egészségügyi Központ Onkológiai Osztály

    Budapest

  • Medical Oncology University Debrecen

    Debrecen

  • University of Pécs

    Pécs

Other trials in Hungary

Poland4 sites

  • Sanodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie, Oddzial Kliniczny Onkologii

    Krakow

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z W-MCO

    Olsztyn

  • Maria Skodowska Curie Memorial Cancer Centre and Institute of Oncology

    Warsaw

  • Dolnoslaskie Centrum Onkologii we Wrocawiu

    Wroclaw

Other trials in Poland

Australia3 sites

  • Flinders Medical Center

    Adelaide

  • Monash Health

    Clayton

  • The Canberra Hospital

    Garran

Other trials in Australia

Canada3 sites

  • Cross Cancer Institute

    Edmonton, Alberta

  • Jewish General Hospital

    Montreal

  • University Health Network

    Toronto, Ontario, M5G 1L7

Other trials in Canada

Netherlands3 sites

  • Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis

    Amsterdam

  • Radboud University Medical Center

    Nijmegen

  • Erasmus Medical Center

    Rotterdam

Other trials in Netherlands

Belgium2 sites

  • Institut Jules Bordet

    Brussels

  • Leuven Cancer Institute

    Leuven

Other trials in Belgium

Czechia2 sites

  • Onkologická klinika Fakultní nemocnice Olomouc

    Olomouc

  • Fackultni Nemocnice v Motole

    Prague

Other trials in Czechia

Austria1 site

  • AKH, Klinik f. Innere Med. I, Onkologie

    Vienna

Other trials in Austria

Singapore1 site

  • National Cancer Centre Singapore

    Singapore

Other trials in Singapore

Sweden1 site

  • Skanes University Hospital

    Lund

Other trials in Sweden

About this study

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)

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.

Conditions
GIST
Being tested
avapritinib, regorafenib
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
Medical subject headings
Gastrointestinal Stromal Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • avapritinibDrug

    Also called BLU-285

    Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously.

  • regorafenibDrug

    Also called Stivarga

    Regorafenib tablets for oral administration. Regorafenib will be dosed at 160 mg once daily for 3 weeks out of every 4 weeks (ie. 3 weeks on/1 week off).

Study groups in NCT03465722
Study groupRoleWhat they receive
avapritinibExperimental300 mg PO QD
Receives: Drug: avapritinib
regorafenibActive comparator160 mg PO QD
Receives: Drug: regorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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.

    Measured: 24 Months

Secondary outcomes (3)

  1. Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1

    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

    Measured: 24 Months

  2. Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib

    To evaluate overall survival (OS) in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib

    Measured: 24 Months

  3. 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

    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.

    Measured: Difference between baseline and week 12 of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2018
  2. Study start26 Mar 2018
  3. Primary completion9 Mar 2020
  4. Study completion15 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
476 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03465722
Sponsor's protocol ID
BLU-285-1303
Status last verified
Sep 2022
First submitted
7 Mar 2018
Last updated
6 Oct 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Expanded access
Available

Publications

  • Serrano C, Bauer S, Gomez-Peregrina D, Kang YK, Jones RL, Rutkowski P, Mir O, Heinrich MC, Tap WD, Newberry K, Grassian A, Shi H, Bialick S, Schoffski P, Pantaleo MA, von Mehren M, Trent JC, George S. Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib. Ann Oncol. 2023 Jul;34(7):615-625. doi: 10.1016/j.annonc.2023.04.006. Epub 2023 Apr 25.

    PubMed 37105265

  • 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.

    PubMed 34343033

  • 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.

    PubMed 30274985

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing avapritinib and regorafenib in people with GIST, run by Blueprint Medicines Corporation at 114 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 114 sites in United States, China, Spain, France, Germany and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: 24 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03465722, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2022.

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