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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03465722
Ethics application status
Date submitted
7/03/2018
Date registered
14/03/2018
Date last updated
6/10/2022

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: regorafenib - 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
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
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
Timepoint [2] 0 0
24 Months
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Difference between baseline and week 12 of treatment

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
Sex
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 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.

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/09/2021
Sample size
Target
Accrual to date
Final
476
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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Nanning
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Bologna
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Candiolo
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Roma
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Manchester
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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/study/NCT03465722
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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Phone 0 0
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Contact person for public queries
Name 0 0
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Contact person for scientific queries



Summary Results

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