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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05566795
Other study ID # DAY101-002
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date February 27, 2023
Est. completion date March 2030

Study information

Verified date June 2024
Source Day One Biopharmaceuticals, Inc.
Contact Day One Clinical Trials Information
Phone 650-484-0899
Email clinicaltrials@dayonebio.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Approximately 400 treatment-naïve low-grade glioma patients 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. Patients will continue tovorafenib until any of the following occurs: disease progression based on Response Assessment in Neuro-Oncology (RANO-LGG) criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study. Arm 2 (Investigator's Choice of SoC Chemotherapy): patients will receive one of 3 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, or vinblastine (VBL) regimen. The choice of SoC chemotherapy regimen will be selected prior to patient randomization. Treatment will continue until completion of therapy or until any of the following occurs: disease progression based on RANO-LGG criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study. Patients who discontinue treatment due to disease progression will have (1) radiographic evidence of progressive disease based on RANO-LGG, as determined by the Investigator and confirmed by the IRC, or (2) clinical progression based on RANO-LGG criteria determined by the Investigator. Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptom with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Patients may continue therapy beyond progressive disease


Recruitment information / eligibility

Status Recruiting
Enrollment 400
Est. completion date March 2030
Est. primary completion date February 2026
Accepts healthy volunteers No
Gender All
Age group N/A to 25 Years
Eligibility 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: - 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


Related Conditions & MeSH terms


Intervention

Drug:
Tovorafenib
Oral type II RAF kinase inhibitor
Chemotherapeutic Agent
Intravenous solution for injection

Locations

Country Name City State
Australia Perth Children's Hospital Nedlands
Australia Women's and Children's Health Network North Adelaide
Australia The Royal Children's Hospital - Children's Cancer Centre Parkville
Australia Sydney Children's Hospital - Randwick Randwick
Australia Children's Health Queensland Hospital and Health Service South Brisbane Queensland
Australia Children's Hospital at Westmead Westmead
Austria Medizinische Universität Wien Innsbruck
Belgium Cliniques Universitaires Saint-Luc Brussel
Belgium Universitair Ziekenhuis Gent Ghent
Belgium Universitair Ziekenhuis Leuven - Campus Gasthuisberg Leuven
Canada Alberta Children's Hospital Calgary Alberta
Canada CHU Sainte-Justine Montréal Quebec
Canada The Montreal Children's Hospital Montréal Quebec
Canada Centre Hospitalier de l'Université Laval et Centre Mère-Enfant Soleil Québec
Canada SickKids - The Hospital for Sick Children Toronto
Canada British Columbia Children's Hospital Vancouver British Columbia
Czechia Fakultní Nemocnice Brno - D?tská Nemocnice Brno
Czechia Motol University Hospital Prague
Denmark Aarhus Universitetshospital Aarhus Midtjylland
Denmark Rigshospitalet Copenhagen
Finland Helsingin yliopistollinen sairaala (HUS) Helsinki
Finland Tampereen Yliopistollinen Sairaala Tampere
France Centre Léon Bérard Lyon
France Hôpital de la Timone Marseille
France Institut Curie Paris
France Gustave Roussy Villejuif
Germany Universitätsklinikum Augsburg Augsburg Bayern
Germany Charité Universitätsmedizin Berlin Berlin
Germany Evangelische Klinikum Bethel (EvKB) Bielefeld
Germany Universitätsklinikum Frankfurt Frankfurt Hessen
Germany Universitätsklinikum Freiburg Freiburg Baden-Württemberg
Germany Universitätsklinikum Hamburg-Eppendorf Hamburg
Germany Universitätsklinikum Heidelberg Heidelberg
Germany Universitätsklinikum Leipzig Leipzig Sachsen
Germany Universitätsklinikum Tübingen Tübingen
Germany Universitätsklinikum Erlangen Ulm
Germany Universitätsklinikum Würzburg Würzburg Bayern
Greece Aghia Sofia General Children's Hospital Athens
Greece Athens General Children's Hospital Athens
Hungary Semmelweis Egyetem Tuzoltó utcai II. Sz. Gyermekgyógyászati Kliniká Budapest
Ireland Children's Health Ireland at Crumlin Crumlin Dublin
Israel Schneider Children's Medical Center of Israel Petah tikva
Israel The Edmond and Lily Safra Children's Hospital Ramat Gan
Italy Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari Bari
Italy Istituto Giannina Gaslini Genova
Italy Fondazione IRCCS - Istituto Nazionale dei Tumori Milano Milan
Italy Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon Napoli
Italy Azienda Ospedale Università di Padova Padova
Italy Ospedale Pediatrico Bambino Gesù Roma Rome
Italy Ospedale Infantile Regina Margherita Torino Turin
Italy Azienda Sanitaria Universitaria Friuli Centrale - P.O. Santa Maria della Misericordia Udine
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital Seoul
Netherlands Prinses Maxima Centrum Kinderoncologie Utrecht
New Zealand Starship Paediatric Blood & Cancer Center Grafton
Norway Oslo Universitetssykehus Oslo
Norway Universitetssykehuset Nord-Norge - Tromsø Tromsø Troms
Singapore SingHealth Group - KK Women's and Children's Hospital Singapore
Slovenia Univerzitetni Klinini Center Ljubljana Ljubljana
Spain Hospital Universitario Cruces Barakaldo
Spain Hospital Sant Joan de Déu Barcelona Barcelona
Spain Hospital Universitari Vall d'Hebrón Barcelona
Spain Hospital Infantil Universitario Niño Jesús Madrid
Spain Hospital Universitario La Paz Madrid
Spain Hospital Universitario Virgen del Rocío Sevilla
Spain Hospital Universitari i Politècnic La Fe Valencia
Sweden Drottning Silvias barn- och ungdomssjukhus Göteborg
Sweden Skånes Universitetssjukhus - Lund Lund
Sweden Astrid Lindgrens Barnsjukhus Solna Stockholm
Switzerland Centre Hospitalier Universitaire Vaudois Lausanne Lausanne
Switzerland Universitaets - Kinderspital Zürich Zurich
United Kingdom Birmingham Women's and Children's NHS Foundation Trust Birmingham England
United Kingdom University Hospitals Bristol and Weston NHS Foundation Trust Bristol
United Kingdom Cambridge University Hospitals NHS Foundation Trust Cambridge
United Kingdom NHS Greater Glasgow and Clyde Glasgow Scotland
United Kingdom Leeds Teaching Hospital NHS Trust Leeds England
United Kingdom Manchester University NHS Foundation Trust Manchester England
United Kingdom The Newcastle Upon Tyne Hospitals NHS Foundation Trust Newcastle Upon Tyne England
United Kingdom Great Ormond Street Hospital for Children Oxford England
United Kingdom The Royal Marsden NHS Foundation Trust Sutton Surrey
United States University of Michigan - - C.S. Mott Children's Hospital Ann Arbor Michigan
United States Children's Healthcare of Atlanta Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Children's of Alabama Birmingham Alabama
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois
United States Cleveland Clinic Main Campus Cleveland Ohio
United States University of Texas Southwestern Medical Center Dallas Texas
United States Duke Cancer Institute Durham North Carolina
United States Texas Children's Hospital Houston Texas
United States Riley Hospital for Children at Indiana University Health Indianapolis Indiana
United States Children's Hospital Los Angeles Los Angeles California
United States New York University Langone Health New York New York
United States Arnold Palmer Hospital for Children Orlando Florida
United States Phoenix Children's Hospital Phoenix Arizona
United States University of Rochester Rochester New York
United States St. Louis Children's Hospital Saint Louis Missouri
United States UCSF Benioff Children's Hospital San Francisco California
United States Seattle Children's Hospital Seattle Washington
United States Children's National Medical Center Washington District of Columbia

Sponsors (2)

Lead Sponsor Collaborator
Day One Biopharmaceuticals, Inc. SIOPe Brain Tumor Group LOGGIC Consortium

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Norway,  Singapore,  Slovenia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 ORR, per RANO-LGG criteria, defined as the proportion of patients with overall confirmed response of complete response (CR) or partial response (PR) Up to 60 months
Secondary Compare the progression-free survival (PFS) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RANO-LGG criteria PFS per RANO-LGG criteria, de?ned as time from randomization to PD or death from any cause Up to 60 months
Secondary Compare the duration of response (DOR) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RANO-LGG criteria DOR per RANO-LGG criteria, de?ned as time from confirmed response to PD or death from any cause for patients with confirmed response Up to 60 months
Secondary Compare the overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy OS, defined as time from randomization up to death from any cause Up to 60 months
Secondary Compare the safety and tolerability of tovorafenib monotherapy versus SoC chemotherapy Type, frequency, and severity of treatment-emergent adverse events Up to 60 months
Secondary Compare the safety and tolerability of tovorafenib monotherapy versus SoC chemotherapy Measured by incidence of clinically significant laboratory abnormalities Up to 60 months
Secondary Evaluate changes in neurological function and adaptive behavior between tovorafenib versus SoC Change from baseline in the Vineland Adaptive Behavior Composite Scales [age-adjusted standard scores range between 20 to 140, with a mean of 100 and standard deviation of 15, and lower scores indicate worse functional outcomes] Up to 60 months
Secondary Compare changes in visual function outcomes of tovorafenib monotherapy versus SoC chemotherapy in patients with optic pathway glioma (OPG) Measured by Teller Acuity Cards® or alternative Up to 60 months
Secondary 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 ORR, de?ned as the proportion of patients with overall con?rmed response per RANO-HGG, RANO-LGG, or RAPNO-LGG criteria. Up to 60 months
Secondary 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 CBR, de?ned as the proportion of patients with radiological tumor stabilization or regression per RANO-LGG, RANO-HGG or RAPNO-LGG criteria, as applicable Up to 60 months
Secondary Compare time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RANO-LGG, RANO-HGG and RAPNO-LGG criteria Measured by the time to ?rst response following initiation of therapy in patients with best overall con?rmed response per RANO-LGG, RANO-HGG or RAPNO-LGG criteria, as applicable Up to 60 months
Secondary Compare the PFS of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO-LGG and RANO-HGG criteria PFS per RANO-HGG or RAPNO-LGG (as applicable), de?ned as time from randomization to progressive disease (PD) or death from any cause Up to 60 months
Secondary Compare the DOR of tovorafenib monotherapy versus SoC chemotherapy as assessed by IRC per RAPNO-LGG and RANO-HGG criteria DOR, de?ned as time from con?rmed response to PD or death from any cause for patients with confirmed response per RANO or RAPNO criteria, as applicable Up to 60 months
Secondary Evaluate the health-related quality of life (HRQoL) in tovorafenib versus SoC chemotherapy using Patient-Reported Outcomes Measurement Information System (PROMIS) test battery Measured by change from baseline in Total Score at 1, 2, 5 years Up to 60 months
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