Clinical trial NCT05566795: DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Low-grade Glioma
Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma
Pediatric Low-grade Glioma
Keywords: Rapidly accelerated fibrosarcoma
RAF alteration glioma
Glioneural tumor
Ojemda
Lead sponsor: Day One Biopharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: SIOPe Brain Tumor Group LOGGIC Consortium
First posted: 2022-10-04
Enrollment: 400
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Tovorafenib versus standard of care chemotherapy
Primary purpose: TREATMENT

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 participants with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring first-line systemic therapy.

Detailed description: Approximately 400 treatment-naïve LGG participants will be randomized 1:1 to either tovorafenib (Arm 1) or an Investigator's choice of SoC chemotherapy (Arm 2).

Arm 1 (tovorafenib): Treatment cycles will repeat every 28 days in the absence of disease progression. Participants will continue tovorafenib until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Arm 2 (Investigator's Choice of SoC Chemotherapy): Participants will receive one of 4 SoC chemotherapy options selected by the treating Investigator: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) regimen, International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) regimen, vinblastine (VBL) regimen, or monthly carboplatin. The choice of SoC chemotherapy regimen will be selected prior to participant randomization. Treatment will continue until completion of therapy or until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Participants who discontinue treatment due to disease progression will have (1) radiographic evidence of disease progression, as determined by the Investigator, or (2) clinical progression, as determined by the Investigator. Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptoms with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Participants may continue therapy beyond progressive disease (PD).

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Objective response rate (ORR) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
Secondary outcomes:
measure: Progression-free survival (PFS) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: Event-free survival (EFS) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: Overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: Number of participants with any treatment-emergent adverse events, and Serious adverse events
timeFrame: Up to 60 months
measure: . Number of participants with clinically significant vital signs and laboratory abnormalities findings
timeFrame: Up to 60 months
measure: Change from baseline in Adaptive Behavior Composite Score (ABS) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Baseline, Year 1, 2 and 5
measure: Change from baseline in the Motor Skills Domain Score of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Baseline, Year 1, 2 and 5
measure: Change from baseline in the Daily Living Domain Score of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Baseline, Year 1, 2 and 5
measure: Change from baseline in the Communication Domain Score of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Baseline, Year 1, 2 and 5
measure: Change from baseline in the Socialization Domain Score of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Baseline, Year 1, 2 and 5
measure: Change in age-adjusted visual acuity (VA) of tovorafenib monotherapy versus SoC chemotherapy in optic pathway glioma (OPG) participants aged < 3 years
timeFrame: Baseline and up to 5 years
measure: Change in best corrected visual acuity of tovorafenib monotherapy versus SoC chemotherapy in OPG participants aged ≥ 3 years
timeFrame: Baseline and up to 5 years
measure: Visual progression-free survival (v-PFS) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: ORR of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: Clinical beneﬁt rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: Time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: PFS of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: EFS of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: Duration of response (DOR) of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Up to 60 months
measure: Change from Baseline in health-related quality of life (HRQoL) total score of tovorafenib monotherapy versus SoC chemotherapy
timeFrame: Baseline, Year 1, 2 and 5
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County Main Campus - Orange
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Health
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: St. Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Scarborough
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan - - C.S. Mott Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: South Brisbane
country: Australia
facility: Children's Health Queensland Hospital and Health Service
state: Queensland
city: Nedlands
country: Australia
facility: Perth Children's Hospital
city: North Adelaide
country: Australia
facility: Women's and Children's Health Network
city: Parkville
country: Australia
facility: The Royal Children's Hospital - Children's Cancer Centre
city: Randwick
country: Australia
facility: Sydney Children's Hospital - Randwick
city: Westmead
country: Australia
facility: Children's Hospital at Westmead
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
state: Tirol
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: São Paulo
country: Brazil
facility: Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC)
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Montréal
country: Canada
facility: The Montreal Children's Hospital
state: Quebec
city: Québec
country: Canada
facility: Centre Hospitalier de l'Université Laval et Centre Mère-Enfant Soleil
city: Toronto
country: Canada
facility: SickKids - The Hospital for Sick Children
city: Brno
country: Czechia
facility: Fakultní Nemocnice Brno - D?tská Nemocnice
city: Prague
country: Czechia
facility: Motol University Hospital
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
state: Midtjylland
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen sairaala (HUS)
city: Tampere
country: Finland
facility: Tampereen Yliopistollinen Sairaala
city: Lille
country: France
facility: Centre de Lutte contre le Cancer - Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Institut Curie
city: Villejuif
country: France
facility: Gustave Roussy
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
state: Baden-Württemberg
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
state: Bayern
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
state: Bayern
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
state: Sachsen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bielefeld
country: Germany
facility: Evangelische Klinikum Bethel (EvKB)
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Athens
country: Greece
facility: Aghia Sofia General Children's Hospital
city: Athens
country: Greece
facility: Athens General Children's Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Tűzoltó utcai II. Sz. Gyermekgyógyászati Kliniká
city: Crumlin
country: Ireland
facility: Children's Health Ireland at Crumlin
state: Dublin
city: Petah tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Ramat Gan
country: Israel
facility: The Edmond and Lily Safra Children's Hospital
city: Milano
country: Italy
facility: Fondazione IRCCS - Istituto Nazionale dei Tumori
state: Milan
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
state: Rome
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita
state: Turin
city: Bari
country: Italy
facility: Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon
city: Padova
country: Italy
facility: Azienda Ospedale Università di Padova
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale - P.O. Santa Maria della Misericordia
city: Amman
country: Jordan
facility: King Hussein Cancer Foundation - King Hussein Cancer Center
state: Muhafazat al-Asima
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum Kinderoncologie
city: Grafton
country: New Zealand
facility: Starship Paediatric Blood & Cancer Center
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge - Tromsø
state: Troms
city: Oslo
country: Norway
facility: Oslo Universitetssykehus
city: Singapore
country: Singapore
facility: SingHealth Group - KK Women's and Children's Hospital
city: Ljubljana
country: Slovenia
facility: Univerzitetni Klinini Center Ljubljana
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu Barcelona
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Göteborg
country: Sweden
facility: Drottning Silvias barn- och ungdomssjukhus
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus - Lund
city: Stockholm
country: Sweden
facility: Astrid Lindgrens Barnsjukhus Solna
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois Lausanne
city: Zurich
country: Switzerland
facility: Universitaets - Kinderspital Zürich
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou Branch
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
state: England
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital NHS Trust
state: England
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
state: England
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
state: England
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
state: England
city: Oxford
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
state: Scotland
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
state: South Yorkshire
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
Study officials:
References: