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

NCT ID: NCT03465722

Last Updated: 2022-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 476 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-26
• Study Completion Date: 2021-09-15

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.

Conditions

GIST

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

avapritinib

300 mg PO QD

Group Type: EXPERIMENTAL

avapritinib

Intervention Type: DRUG

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

regorafenib

160 mg PO QD

Group Type: ACTIVE_COMPARATOR

regorafenib

Intervention Type: DRUG

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).

Interventions

avapritinib

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

Intervention Type: DRUG

regorafenib

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).

Intervention Type: DRUG

Other Intervention Names

BLU-285; Stivarga

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Blueprint Medicines Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic Cancer Center

Phoenix, Arizona, United States

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, United States

University of Colorado Hospital

Aurora, Colorado, United States

Rocky Mountain Cancer Centers

Boulder, Colorado, United States

Washington Hospital Center - Oncology and Hematology

Washington D.C., District of Columbia, United States

Mayo Clinic Cancer Center

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Northside Hospital

Atlanta, Georgia, 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

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Washington University in Saint Louis

St Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

OHSU - Knight Cancer Institute

Portland, Oregon, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Tennessee Oncology

Nashville, Tennessee, United States

USO - Texas Oncology

Dallas, Texas, United States

Texas Oncology - Denton South

Denton, Texas, United States

University of Texas MD Anderson

Houston, Texas, United States

Texas Oncology - Waco

Waco, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Summit Cancer Centers

Spokane, Washington, United States

Medical College of Wisconsin - Froedtert Hospital

Milwaukee, Wisconsin, United States

Flinders Medical Center

Adelaide, , Australia

Monash Health

Clayton, , Australia

The Canberra Hospital

Garran, , Australia

AKH, Klinik f. Innere Med. I, Onkologie

Vienna, , Austria

Institut Jules Bordet

Brussels, , Belgium

Leuven Cancer Institute

Leuven, , Belgium

Cross Cancer Institute

Edmonton, Alberta, Canada

University Health Network

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, , Canada

Beijing Cancer Hospital

Beijing, , China

Chinese PLA General Hospital

Beijing, , China

West China Hospital Sichuan University

Chengdu, , China

The First Affiliated Hospital of Chongqing Medical University

Chongqing, , 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

The First Affiliated Hospital, Zhejiang University

Hangzhou, , China

Harbin Medical University Cancer Hospital

Harbin, , China

The First Affiliated Hospital of Nanchang Medical University

Nanchang, , China

Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College

Nanning, , China

The Affiliated Hospital of Qingdao University

Qingdao, , China

Fudan University Shanghai Cancer Center

Shanghai, , China

Fudan University Zhongshan Hospital

Shanghai, , China

Shanghai Jiaotong University School of Medicine, Renji Hospital

Shanghai, , China

Liaoning Cancer Hospital & Institute

Shenyang, , China

Tianjin Cancer Hospital

Tianjin, , China

Affiliated Cancer Hospital of Xinjiang Medical University

Ürümqi, , China

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

Wuhan, , China

Onkologická klinika Fakultní nemocnice Olomouc

Olomouc, , Czechia

Fackultni Nemocnice v Motole

Prague, , Czechia

Institut Bergonié

Bordeaux, , France

Centre Oscar Lambret

Lille, , France

UNICANCER - Lyon, Centre Léon-Bérard

Lyon, , France

Institute Paoli Calmettes

Marseille, , France

La Timone University Hospital

Marseille, , France

Institut Curie

Paris, , France

Centre Rene Gauducheau

Saint-Herblain, , France

Gustave Roussy Cancer Campus

Villejuif, , France

HELIOS Klinikum Bad Saarow

Bad Saarow, , Germany

HELIOS Klinikum Berlin-Buch

Berlin, , Germany

Medizinische Fakultät Carl Gustav Carus

Dresden, , Germany

Universitaetsklindum Essen

Essen, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Studienzentrale GbR Lübecker Onkologische Schwerpunktpraxis Dres. med. Uthgenannt

Lübeck, , Germany

Rupercht-Karls-Universitaet Heidelberg

Mannheim, , Germany

Fovarosi Onkormanyzat Szent Laszlo Korhaz

Budapest, , Hungary

Magyar Honvédség Egészségügyi Központ Onkológiai Osztály

Budapest, , Hungary

Medical Oncology University Debrecen

Debrecen, , Hungary

University of Pécs

Pécs, , Hungary

Azienda Ospedaliero Universitaria Sant'Orsola Malpighi

Bologna, , Italy

Candiolo Cancer Institute - FPO, IRCCS

Candiolo, , Italy

AOUC Azienda Ospedaliero - Universitaria Careggi

Florence, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori Milano

Milan, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

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

Palermo, , Italy

Campus Bio-Medico - Oncology Medica

Roma, , Italy

Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Radboud University Medical Center

Nijmegen, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

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

Krakow, , Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z W-MCO

Olsztyn, , Poland

Maria Skodowska Curie Memorial Cancer Centre and Institute of Oncology

Warsaw, , Poland

Dolnoslaskie Centrum Onkologii we Wrocawiu

Wroclaw, , Poland

National Cancer Centre Singapore

Singapore, , Singapore

Ajou University Hospital

Suwon, Gyeong Gi-do, South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Institut Català d'Oncologia - Hospital Duran i Reynals

Barcelona, , Spain

Vall d'Hebron

Barcelona, , Spain

Hospital La Paz

Madrid, , Spain

Hospital Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Puerta de Hierro

Madrid, , Spain

Hospital Virgen del Rocio

Seville, , Spain

Fundacion Instituto Valenciano de Oncologia, Servicio de Oncologia

Valencia, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Skanes University Hospital

Lund, , Sweden

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

The Royal Marsden Hospital

London, , United Kingdom

Guy's Hospital

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; China; Czechia; France; Germany; Hungary; Italy; Netherlands; Poland; Singapore; South Korea; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37105265 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34343033 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30274985 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BLU-285-1303

Identifier Type: -

Identifier Source: org_study_id