Summary

Eligibility
for people ages up to 25 years (full criteria)
Location
at UCSF
Dates
study started
completion around

Description

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.

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

Details

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

Keywords

Low-grade Glioma, Glioma, Antineoplastic Agents, Tovorafenib, Chemotherapeutic Agent

Eligibility

You can join if…

Open to people ages up to 25 years

  • 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

You CAN'T join if...

  • 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

Locations

  • UCSF Benioff Children's Hospital accepting new patients
    San Francisco California 94158 United States
  • Children's Hospital Los Angeles accepting new patients
    Los Angeles California 90027 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Day One Biopharmaceuticals, Inc.
ID
NCT05566795
Phase
Phase 3 Glioma Research Study
Study Type
Interventional
Participants
Expecting 400 study participants
Last Updated