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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04775485




Registration number
NCT04775485
Ethics application status
Date submitted
3/02/2021
Date registered
1/03/2021
Date last updated
10/04/2025

Titles & IDs
Public title
A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors
Scientific title
FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors
Secondary ID [1] 0 0
DAY101-001/PNOC026
Universal Trial Number (UTN)
Trial acronym
FIREFLY-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low-grade Glioma 0 0
Advanced Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tovorafenib

Experimental: Arm 1: Low-Grade Glioma - Participants with recurrent or progressive low-grade glioma will receive 420 milligrams/meters square (mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline body surface area (BSA).

Experimental: Arm 2: Low-Grade Glioma Expanded Access - Participants with recurrent or progressive low-grade glioma will receive 420 mg/m\^2 of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA.

Experimental: Arm 3: Advanced Solid Tumor - Participants with advanced solid tumors will receive 420 mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA.


Treatment: Drugs: Tovorafenib
Tovorafenib is an oral Type II RAF kinase inhibitor available in 100 mg immediate-release tablet or 25 mg/milliliter (mL) powder for reconstitution.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Arm 1: Overall response rate
Timepoint [1] 0 0
Up to 48 months
Primary outcome [2] 0 0
Arm 2: Number of participants reporting adverse events
Timepoint [2] 0 0
Up to 48 months
Primary outcome [3] 0 0
Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters
Timepoint [3] 0 0
Up to 48 months
Primary outcome [4] 0 0
Arm 2: Number of participants with clinically significant changes in hematology parameters
Timepoint [4] 0 0
Up to 48 months
Primary outcome [5] 0 0
Arm 3: Overall response rate
Timepoint [5] 0 0
Up to 48 months
Secondary outcome [1] 0 0
Arm 1 and 3: Number of participants reporting adverse events
Timepoint [1] 0 0
Up to 48 months
Secondary outcome [2] 0 0
Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters
Timepoint [2] 0 0
Up to 48 months
Secondary outcome [3] 0 0
Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [4] 0 0
Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib
Timepoint [4] 0 0
Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1
Secondary outcome [5] 0 0
Arm 1: Minimum drug concentration (Cmin)
Timepoint [5] 0 0
Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1
Secondary outcome [6] 0 0
Arm 1: Change from Baseline QT interval corrected for heart rate by Fridericia's formula (?QTcF)
Timepoint [6] 0 0
Baseline to 48 months
Secondary outcome [7] 0 0
Arm 1: Change from Baseline PR interval (?PR)
Timepoint [7] 0 0
Baseline to 48 months
Secondary outcome [8] 0 0
Arm 1: Change from Baseline QRS interval (?QRS)
Timepoint [8] 0 0
Baseline to 48 months
Secondary outcome [9] 0 0
Arm 1: Change from baseline heart rate (?HR)
Timepoint [9] 0 0
Baseline to 48 months
Secondary outcome [10] 0 0
Arm 1: Change in electrocardiogram (ECG) waveform morphology
Timepoint [10] 0 0
Baseline to 48 months
Secondary outcome [11] 0 0
Arm 1 and Arm 2: Overall response rate
Timepoint [11] 0 0
Up to 48 months
Secondary outcome [12] 0 0
Arm 1, Arm 2 and Arm 3: Overall response rate in Pediatric participants
Timepoint [12] 0 0
Up to 48 months
Secondary outcome [13] 0 0
Arm 1, Arm 2 and Arm 3: duration of progression-free survival (PFS)
Timepoint [13] 0 0
Up to 48 months
Secondary outcome [14] 0 0
Arm 1, Arm 2 and Arm 3: Duration of response (DOR)
Timepoint [14] 0 0
Up to 48 months
Secondary outcome [15] 0 0
Arm 1, Arm 2 and Arm 3: Time to response (TTR)
Timepoint [15] 0 0
Up to 48 months
Secondary outcome [16] 0 0
Arm 1, Arm 2 and Arm 3: Clinical benefit rate (CBR)
Timepoint [16] 0 0
Up to 48 months
Secondary outcome [17] 0 0
Arm 1 and Arm 2: Duration of overall survival
Timepoint [17] 0 0
Up to 48 months
Secondary outcome [18] 0 0
Arm 1: Change from baseline in best corrected visual acuity (BCVA) outcomes
Timepoint [18] 0 0
Baseline to 48 months
Secondary outcome [19] 0 0
Arm 1: Changes in molecular analysis of cells obtained from archival tissue
Timepoint [19] 0 0
At Screening

Eligibility
Key inclusion criteria
* Low Grade Glioma & Low-Grade Glioma Extension: a relapsed or progressive LGG with documented known activating BRAF alteration.
* Advanced Solid Tumor: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion.
* Participants must have histopathologic verification of malignancy at either original diagnosis or relapse.
* Must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression.
* Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria
Minimum age
6 Months
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant's tumor has additional previously-known activating molecular alterations.
* Participant has symptoms of without radiographically recurrent or radiographically progressive disease.
* Known or suspected diagnosis of neurofibromatosis type 1 (NF-1) via genetic testing or current diagnostic criteria.

Other inclusion/exclusion criteria as stipulated by protocol may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 2
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
22/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/05/2027
Actual
Sample size
Target
141
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Queensland Children's Hospital - Brisbane
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Perth Children's Hospital - Perth
Recruitment hospital [4] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [5] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
WA 6009 - Perth
Recruitment postcode(s) [4] 0 0
NSW 2031 - Randwick
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Denmark
State/province [16] 0 0
Copenhagen
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Heidelberg
Country [19] 0 0
Israel
State/province [19] 0 0
Haifa
Country [20] 0 0
Israel
State/province [20] 0 0
Petah Tikva
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Netherlands
State/province [23] 0 0
Utrecht
Country [24] 0 0
Singapore
State/province [24] 0 0
Singapore
Country [25] 0 0
Switzerland
State/province [25] 0 0
Zürich
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Day One Biopharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Pacific Pediatric Neuro-Oncology Consortium
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Day One Biopharmaceuticals, Inc.
Address 0 0
Country 0 0
Phone 0 0
650-484-0899
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04775485