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

GIST Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03465722
• Other study ID #: BLU-285-1303
• Status: Completed
• Phase: Phase 3
• Start date: March 26, 2018
• Est. completion date: September 15, 2021

Study information

• Verified date: September 2022
• Source: Blueprint Medicines Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 476
• Est. completion date: September 15, 2021
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (PDGRFa) 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.

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors
• GIST

Intervention

Drug:
• avapritinib
Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously.
• 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).

Locations

Country	Name	City	State
Australia	Flinders Medical Center	Adelaide
Australia	Monash Health	Clayton
Australia	The Canberra Hospital	Garran
Austria	AKH, Klinik f. Innere Med. I, Onkologie	Wien
Belgium	Institut Jules Bordet	Brussels
Belgium	Leuven Cancer Institute	Leuven
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Jewish General Hospital	Montréal
Canada	University Health Network	Toronto	Ontario
China	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
Czechia	Onkologická klinika Fakultní nemocnice Olomouc	Olomouc
Czechia	Fackultni Nemocnice v Motole	Praha
France	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
Germany	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	Lubeck
Germany	Rupercht-Karls-Universitaet Heidelberg	Mannheim
Hungary	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
Italy	Azienda Ospedaliero Universitaria Sant'Orsola Malpighi	Bologna
Italy	Candiolo Cancer Institute - FPO, IRCCS	Candiolo
Italy	AOUC Azienda Ospedaliero - Universitaria Careggi	Firenze
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori Milano	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Universita degli Studi di Palermo - Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Campus Bio-Medico - Oncology Medica	Roma
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyeong Gi-do
Netherlands	Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	Erasmus Medical Center	Rotterdam
Poland	Sanodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie, Oddzial Kliniczny Onkologii	Kraków
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z W-MCO	Olsztyn
Poland	Maria Skodowska Curie Memorial Cancer Centre and Institute of Oncology	Warszawa
Poland	Dolnoslaskie Centrum Onkologii we Wrocawiu	Wroclaw
Singapore	National Cancer Centre Singapore	Singapore
Spain	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	Sevilla
Spain	Fundacion Instituto Valenciano de Oncologia, Servicio de Oncologia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Skanes University Hospital	Lund
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Guy's Hospital	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northside Hospital	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Rocky Mountain Cancer Centers	Boulder	Colorado
United States	Northwestern Medicine	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	USO - Texas Oncology	Dallas	Texas
United States	Texas Oncology - Denton South	Denton	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Texas MD Anderson	Houston	Texas
United States	Mayo Clinic Cancer Center	Jacksonville	Florida
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin - Froedtert Hospital	Milwaukee	Wisconsin
United States	Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Cancer Center	Phoenix	Arizona
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	OHSU - Knight Cancer Institute	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Washington University in Saint Louis	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCLA Hematology/Oncology - Santa Monica	Santa Monica	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Summit Cancer Centers	Spokane	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Texas Oncology - Waco	Waco	Texas
United States	Washington Hospital Center - Oncology and Hematology	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Blueprint Medicines Corporation

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Czechia,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Singapore,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 Months
Secondary	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	24 Months
Secondary	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	24 Months
Secondary	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.	Difference between baseline and week 12 of treatment