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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05566795




Registration number
NCT05566795
Ethics application status
Date submitted
16/09/2022
Date registered
4/10/2022
Date last updated
10/06/2024

Titles & IDs
Public title
DAY101 vs. Standard of Care Chemotherapy in Pediatric Patients With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
Scientific title
LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy
Secondary ID [1] 0 0
DAY101-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low-grade Glioma 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
Treatment: Drugs - Chemotherapeutic Agent

Experimental: Arm #1 - Tovorafenib

Active Comparator: Arm #2 - Investigator's choice of one of the following current standard of care for pediatric patients with low-grade gliomas:
Children's Oncology Group - Vincristine/Carboplatin (COG-V/C)
International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C)
Vinblastine (VBL)


Treatment: Drugs: Tovorafenib
Oral type II RAF kinase inhibitor

Treatment: Drugs: Chemotherapeutic Agent
Intravenous solution for injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Compare the objective response rate (ORR) assessed per RANO-LGG criteria by Independent Review Committee (IRC) of tovorafenib monotherapy versus standard of care (SoC) chemotherapy
Timepoint [1] 0 0
Up to 60 months
Secondary outcome [1] 0 0
Compare the progression-free survival (PFS) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RANO-LGG criteria
Timepoint [1] 0 0
Up to 60 months
Secondary outcome [2] 0 0
Compare the duration of response (DOR) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RANO-LGG criteria
Timepoint [2] 0 0
Up to 60 months
Secondary outcome [3] 0 0
Compare the overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy
Timepoint [3] 0 0
Up to 60 months
Secondary outcome [4] 0 0
Compare the safety and tolerability of tovorafenib monotherapy versus SoC chemotherapy
Timepoint [4] 0 0
Up to 60 months
Secondary outcome [5] 0 0
Compare the safety and tolerability of tovorafenib monotherapy versus SoC chemotherapy
Timepoint [5] 0 0
Up to 60 months
Secondary outcome [6] 0 0
Evaluate changes in neurological function and adaptive behavior between tovorafenib versus SoC
Timepoint [6] 0 0
Up to 60 months
Secondary outcome [7] 0 0
Compare changes in visual function outcomes of tovorafenib monotherapy versus SoC chemotherapy in patients with optic pathway glioma (OPG)
Timepoint [7] 0 0
Up to 60 months
Secondary outcome [8] 0 0
Compare the ORR of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-HGG and Response Assessment in Pediatric Neuro-Oncology (RAPNO-LGG) criteria
Timepoint [8] 0 0
Up to 60 months
Secondary outcome [9] 0 0
Compare the clinical bene?t rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-LGG, RANO-HGG and RAPNO-LGG criteria
Timepoint [9] 0 0
Up to 60 months
Secondary outcome [10] 0 0
Compare time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-LGG, RANO-HGG and RAPNO-LGG criteria
Timepoint [10] 0 0
Up to 60 months
Secondary outcome [11] 0 0
Compare the PFS of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO-LGG and RANO-HGG criteria
Timepoint [11] 0 0
Up to 60 months
Secondary outcome [12] 0 0
Compare the DOR of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO-LGG and RANO-HGG criteria
Timepoint [12] 0 0
Up to 60 months
Secondary outcome [13] 0 0
Evaluate the health-related quality of life (HRQoL) in tovorafenib versus SoC chemotherapy using Patient-Reported Outcomes Measurement Information System (PROMIS) test battery
Timepoint [13] 0 0
Up to 60 months

Eligibility
Key inclusion criteria
- Less than 25 years of age with LGG with known activating RAF alteration

- Histopathologic diagnosis of glioma or glioneuronal tumor

- At least one measurable lesion as defined by RANO criteria

- Meet indication for first-line systemic therapy
Minimum age
No limit
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient has any of the following tumor-histological findings:

1. Schwannoma

2. Subependymal giant cell astrocytoma (Tuberous Sclerosis)

3. Diffuse intrinsic pontine glioma, even if histologically diagnosed as World
Health Organization (WHO) Grade I-II

- Patient's tumor has additional pathogenic molecular alterations, including but not
limited to a) IDH 1/2 mutation, b) Histone H3 mutation, and c) NF-1 loss of function
alteration.

- Known or suspected diagnosis of neurofibromatosis Type 1 or 2 (NF-1/NF-2)

- Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy,
oral/intravenous targeted therapy) including radiation

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
27/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2030
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Children's Health Queensland Hospital and Health Service - South Brisbane
Recruitment hospital [2] 0 0
Perth Children's Hospital - Nedlands
Recruitment hospital [3] 0 0
Women's and Children's Health Network - North Adelaide
Recruitment hospital [4] 0 0
The Royal Children's Hospital - Children's Cancer Centre - Parkville
Recruitment hospital [5] 0 0
Sydney Children's Hospital - Randwick - Randwick
Recruitment hospital [6] 0 0
Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
5006 - North Adelaide
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
2031 - Randwick
Recruitment postcode(s) [6] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
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California
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Colorado
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District of Columbia
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United States of America
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Florida
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United States of America
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Georgia
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Illinois
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Indiana
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Massachusetts
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Michigan
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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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Texas
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Washington
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Austria
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Innsbruck
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Belgium
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Brussel
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Belgium
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Ghent
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Belgium
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Leuven
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Canada
State/province [22] 0 0
Alberta
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Canada
State/province [23] 0 0
British Columbia
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Canada
State/province [24] 0 0
Quebec
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Canada
State/province [25] 0 0
Québec
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Canada
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Toronto
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Czechia
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Brno
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Czechia
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Prague
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Midtjylland
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Denmark
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Copenhagen
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Finland
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Helsinki
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Tampere
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Lyon
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Paris
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France
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Villejuif
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Germany
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Baden-Württemberg
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Germany
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Bayern
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Germany
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Hessen
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Sachsen
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Berlin
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Bielefeld
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Hamburg
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Heidelberg
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Tübingen
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Ulm
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Greece
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Athens
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Hungary
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Budapest
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Ireland
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Dublin
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Israel
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Petah tikva
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Israel
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Ramat Gan
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Italy
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Milan
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Italy
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Rome
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Italy
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Turin
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Italy
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Bari
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Italy
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Genova
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Italy
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Napoli
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Italy
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Padova
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Italy
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Udine
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Korea, Republic of
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Seoul
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Netherlands
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Utrecht
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New Zealand
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Grafton
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Norway
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Troms
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Norway
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Oslo
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Singapore
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Singapore
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Slovenia
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Ljubljana
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Spain
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Barakaldo
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Spain
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Barcelona
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Madrid
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Spain
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Sevilla
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Spain
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Valencia
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Sweden
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Göteborg
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Sweden
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Lund
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Sweden
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Stockholm
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Switzerland
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Lausanne
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Switzerland
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Zurich
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United Kingdom
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England
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United Kingdom
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Scotland
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United Kingdom
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Surrey
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Bristol
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United Kingdom
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Cambridge

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
SIOPe Brain Tumor Group LOGGIC Consortium
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a 2-arm, randomized, open-label, multicenter, global, Phase 3 trial to evaluate the
efficacy, safety, and tolerability of tovorafenib monotherapy versus standard of care (SoC)
chemotherapy in patients with pediatric low-grade glioma (LGG) harboring an activating
rapidly accelerated fibrosarcoma (RAF) alteration requiring front-line systemic therapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05566795
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 Clinical Trials Information
Address 0 0
Country 0 0
Phone 0 0
650-484-0899
Fax 0 0
Email 0 0
clinicaltrials@dayonebio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05566795