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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03465722




Registration number
NCT03465722
Ethics application status
Date submitted
7/03/2018
Date registered
14/03/2018
Date last updated
30/05/2019

Titles & IDs
Public title
(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST
Scientific 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)
Secondary ID [1] 0 0
BLU-285-1303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
GIST 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - avapritinib
Treatment: Drugs - regorafenib

Experimental: avapritinib - 300 mg PO QD

Active Comparator: regorafinib - 160 mg PO QD


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

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
24 Months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
24 Months
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
60 Months
Secondary outcome [3] 0 0
European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30) physical functioning score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib - To evaluate the mean change from baseline to week 12 in European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30) physical functioning score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib
Timepoint [3] 0 0
12 Weeks
Secondary outcome [4] 0 0
EORTC-QLQ-C30 pain score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib - To evaluate the mean change from baseline to week 12 in EORTC-QLQ-C30 pain score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib
Timepoint [4] 0 0
12 Weeks
Secondary outcome [5] 0 0
EORTC-QLQ-C30 role functioning score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib - To evaluate the mean change from baseline to week 12 in EORTC-QLQ-C30 role functioning score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib
Timepoint [5] 0 0
12 Weeks
Secondary outcome [6] 0 0
EORTC-QLQ-C30 appetite loss score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib - To evaluate the mean change from baseline to week 12 in EORTC-QLQ-C30 appetite loss score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib
Timepoint [6] 0 0
12 Weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 2 weeks before
randomization.

5. Patients with clinically significant cardiovascular disease, uncontrolled
thromboembolic disease, or significant risk of bleeding.

6. Patients who have a non-healing wound, ulcer, gastrointestinal perforation, or bone
fracture.

7. Patients who have poor organ function as defined by laboratory parameters specified in
the protocol.

8. Patients who have received neutrophil growth factor support within 14 days of
randomization.

9. Patients who require therapy with a concomitant medication that is a strong inhibitor
or strong inducer of CYP3A4.

10. Patients who have had a major surgical procedure within 14 days of randomization.
Patient has significant traumatic injury within 28 days before randomization.

11. Patients who have a history of another primary malignancy that has been diagnosed or
required therapy within 3 years before randomization.

12. Patients who have a history of a seizure disorder requiring anti-seizure medication.

13. Patients who have metastases to the brain.

14. Patients who have a QT interval corrected using Fridericia's formula (QTcF) of > 450
msec.

15. Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from
sexual intercourse or employ highly effective contraception from the time of
randomization and for at least 30 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 randomization and for at least 90 days
after the last dose of study drug.

16. Women who are pregnant.

17. Women who are breastfeeding.

18. 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Center - Adelaide
Recruitment hospital [2] 0 0
Monash Health - Clayton
Recruitment hospital [3] 0 0
The Canberra Hospital - Garran
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Garran
Recruitment outside Australia
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United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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Colorado
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District of Columbia
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Florida
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Georgia
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Illinois
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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United States of America
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Tennessee
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United States of America
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Texas
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Utah
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Washington
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United States of America
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Wisconsin
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Austria
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Wien
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Belgium
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Brussels
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Belgium
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Leuven
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Canada
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Alberta
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Canada
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Ontario
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Canada
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Montréal
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Czechia
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Olomouc
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Czechia
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Praha
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France
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Bordeaux
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France
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Lille
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France
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Lyon
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France
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Marseille
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France
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Saint-Herblain
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France
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Villejuif
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Germany
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Bad Saarow
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Essen
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Germany
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Frankfurt
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Germany
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Lubeck
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Germany
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Mannheim
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Pécs
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Italy
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Bologna
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Italy
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Candiolo
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Italy
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Firenze
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Italy
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Milano
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Italy
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Palermo
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Italy
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Roma
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Korea, Republic of
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Gyeong Gi-do
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Korea, Republic of
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Seoul
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Netherlands
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Nijmegen
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Netherlands
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Rotterdam
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Poland
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Olsztyn
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Warszawa
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Wroclaw
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Singapore
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Singapore
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Barcelona
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Madrid
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Sevilla
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Spain
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Zaragoza
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Sweden
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Lund
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United Kingdom
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Glasgow
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London
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Manchester
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United Kingdom
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Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Blueprint Medicines Corporation
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03465722
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Blueprint Medicines
Address 0 0
Country 0 0
Phone 0 0
617-714-6707
Fax 0 0
Email 0 0
studydirector@blueprintmedicines.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03465722