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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT05566795
Ethics application status
Date submitted
16/09/2022
Date registered
4/10/2022
Date last updated
24/06/2025

Titles & IDs
Public title
DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants 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
2022-001363-27
Secondary ID [2] 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
Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma 0 0
Pediatric Low-grade Glioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

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

Experimental: Tovorafenib -

Active comparator: Investigator's choice of Standard of care therapy -


Treatment: Drugs: Tovorafenib
Oral Tablet Powder for Oral Suspension

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
Objective response rate (ORR) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [1] 0 0
ORR assessed per Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria by Independent Review Committee (IRC), and defined as the proportion of participants with overall confirmed response of complete response (CR), partial response (PR), or minor response (MR).
Timepoint [1] 0 0
Up to 60 months
Secondary outcome [1] 0 0
Progression-free survival (PFS) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [1] 0 0
PFS assessed per RAPNO criteria by IRC, and de?ned as time from randomization to PD or death from any cause, whichever comes first.
Timepoint [1] 0 0
Up to 60 months
Secondary outcome [2] 0 0
Event-free survival (EFS) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [2] 0 0
EFS assessed per RAPNO criteria by IRC, de?ned as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.
Timepoint [2] 0 0
Up to 60 months
Secondary outcome [3] 0 0
Overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [3] 0 0
Overall survival is defined as time from randomization up to death from any cause.
Timepoint [3] 0 0
Up to 60 months
Secondary outcome [4] 0 0
Number of participants with any treatment-emergent adverse events, and Serious adverse events
Assessment method [4] 0 0
Type, frequency, and severity of adverse events of tovorafenib monotherapy versus SoC chemotherapy will be assessed.
Timepoint [4] 0 0
Up to 60 months
Secondary outcome [5] 0 0
. Number of participants with clinically significant vital signs and laboratory abnormalities findings
Assessment method [5] 0 0
Type, frequency, and severity of vital signs and laboratory abnormalities of tovorafenib monotherapy versus SoC chemotherapy will be assessed.
Timepoint [5] 0 0
Up to 60 months
Secondary outcome [6] 0 0
Change from baseline in Adaptive Behavior Composite Score (ABS) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [6] 0 0
Adaptive behavior Composite Score will be evaluated using domain scores collected from the comprehensive Vineland III Adaptive Behavior Scale (VABS).
Timepoint [6] 0 0
Baseline, Year 1, 2 and 5
Secondary outcome [7] 0 0
Change from baseline in the Motor Skills Domain Score of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [7] 0 0
The motor skills (gross and fine) will be assessed using the Motor Skills Score domain of the VABS in pediatric participants.
Timepoint [7] 0 0
Baseline, Year 1, 2 and 5
Secondary outcome [8] 0 0
Change from baseline in the Daily Living Domain Score of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [8] 0 0
The daily living (personal, domestic and community) will be assessed using Daily Living Domain Score of VABS.
Timepoint [8] 0 0
Baseline, Year 1, 2 and 5
Secondary outcome [9] 0 0
Change from baseline in the Communication Domain Score of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [9] 0 0
The communication skills (receptive, expressive and written) will be assessed using Communication Domain Score of VABS.
Timepoint [9] 0 0
Baseline, Year 1, 2 and 5
Secondary outcome [10] 0 0
Change from baseline in the Socialization Domain Score of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [10] 0 0
The socialization skills (Interpersonal relationships, play and leisure time and coping skills) will be assessed using Socialization Domain Score of VABS.
Timepoint [10] 0 0
Baseline, Year 1, 2 and 5
Secondary outcome [11] 0 0
Change in age-adjusted visual acuity (VA) of tovorafenib monotherapy versus SoC chemotherapy in optic pathway glioma (OPG) participants aged < 3 years
Assessment method [11] 0 0
Visual acuity testing using current age-appropriate testing methodology will be performed for all participants at Screening. For participants with OPG or an underlying visual deficit related to the primary malignancy, visual acuity testing will be performed every time participants have a radiographic response assessment. Assessments will be performed in each eye separately at a recommended testing distance of 3 meters.
Timepoint [11] 0 0
Baseline and up to 5 years
Secondary outcome [12] 0 0
Change in best corrected visual acuity of tovorafenib monotherapy versus SoC chemotherapy in OPG participants aged = 3 years
Assessment method [12] 0 0
Visual acuity assessments to be performed by an ophthalmologist or another qualified site clinical personnel.
Timepoint [12] 0 0
Baseline and up to 5 years
Secondary outcome [13] 0 0
Visual progression-free survival (v-PFS) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [13] 0 0
Visual progression-free survival is defined as the time from start of treatment to visual event for OPG participants aged = 3 years.
Timepoint [13] 0 0
Up to 60 months
Secondary outcome [14] 0 0
ORR of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [14] 0 0
ORR, defined as the proportion of participants with overall confirmed response per Response Assessment in Neuro-Oncology for High-Grade Glioma (RANO-HGG) criteria (CR or PR) and RANO-LGG criteria (CR, PR, or MR), as applicable.
Timepoint [14] 0 0
Up to 60 months
Secondary outcome [15] 0 0
Clinical bene?t rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [15] 0 0
CBR, de?ned as the proportion of participants with radiological tumor stabilization or regression per RANO-LGG (CR, PR, MR, or SD lasting 12 months or more), RANO-HGG (CR, PR, or SD lasting 12 months or more) or RAPNO criteria (CR, PR, MR or SD lasting 12 months or more), as applicable.
Timepoint [15] 0 0
Up to 60 months
Secondary outcome [16] 0 0
Time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [16] 0 0
TTR, measured by the time following randomization to ?rst imaging of tumor response that was subsequently con?rmed per RANO-HGG criteria (CR or PR), RANO-LGG criteria (CR, or PR, or MR), or RAPNO criteria (CR, PR, or MR), as applicable.
Timepoint [16] 0 0
Up to 60 months
Secondary outcome [17] 0 0
PFS of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [17] 0 0
PFS per RANO-HGG or RANO-LGG criteria (as applicable), de?ned as time from randomization to PD or death from any cause, whichever occurs first.
Timepoint [17] 0 0
Up to 60 months
Secondary outcome [18] 0 0
EFS of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [18] 0 0
EFS per RANO-HGG or RANO-LGG criteria (as applicable), defined as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.
Timepoint [18] 0 0
Up to 60 months
Secondary outcome [19] 0 0
Duration of response (DOR) of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [19] 0 0
DOR, de?ned as time from first imaging of tumor response per RANO-LGG, RANO-HGG or RAPNO criteria, as applicable, that was subsequently confirmed to radiographic PD or death from any cause, whichever comes first.
Timepoint [19] 0 0
Up to 60 months
Secondary outcome [20] 0 0
Change from Baseline in health-related quality of life (HRQoL) total score of tovorafenib monotherapy versus SoC chemotherapy
Assessment method [20] 0 0
The Patient-Reported Outcomes Measurement Information System (PROMIS®) Pediatric/Parent Proxy Profile 49 v2.0 will be used to assess mental and social HRQoL.
Timepoint [20] 0 0
Baseline, Year 1, 2 and 5

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
* Participant 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
* Participant's tumor has additional pathogenic molecular alterations, including but not limited to a) isocitrate dehydrogenase (IDH) 1/2 mutation, b) Histone H3 mutation, and c) neurofibromatosis Type 1 (NF-1) loss of function alteration.
* Known or suspected diagnosis of NF-1/ neurofibromatosis Type 2 (NF-2).
* Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/IV 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
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
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United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
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Georgia
Country [9] 0 0
United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Maine
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United States of America
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nebraska
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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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Wisconsin
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Austria
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Tirol
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Austria
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Wien
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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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Brazil
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São Paulo
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Alberta
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British Columbia
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Ontario
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Québec
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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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Copenhagen
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Finland
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Helsinki
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Lille
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Paris
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Villejuif
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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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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Sachsen
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Germany
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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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Petah tikva
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Israel
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Ramat Gan
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Milan
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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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Jordan
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Muhafazat al-Asima
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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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Taiwan
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Taipei
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Taiwan
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Taoyuan
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United Kingdom
State/province [90] 0 0
England
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United Kingdom
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Hampshire
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United Kingdom
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Northern Ireland
Country [93] 0 0
United Kingdom
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Scotland
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United Kingdom
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South Yorkshire
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United Kingdom
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Surrey
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United Kingdom
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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.
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
SIOPe Brain Tumor Group LOGGIC Consortium
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 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
Email 0 0
clinicaltrials@dayonebio.com
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05566795