DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
Purpose
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.
Conditions
- Low-grade Glioma
- Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma
- Pediatric Low-grade Glioma
Eligibility
- Eligible Ages
- Under 25 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Tovorafenib versus standard of care chemotherapy
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Tovorafenib |
|
|
|
Active Comparator Investigator's choice of Standard of care therapy |
|
Recruiting Locations
Birmingham 4049979, Alabama 4829764 35233
Phoenix 5308655, Arizona 5551752 85016
Los Angeles 5368361, California 5332921 90027
Orange 5379513, California 5332921 92868
Palo Alto 5380748, California 5332921 94304
San Francisco 5391959, California 5332921 94158
Aurora 5412347, Colorado 5417618 80045
Hartford 4835797, Connecticut 4831725 06106-3322
Washington D.C. 4140963, District of Columbia 4138106 20010
Gainesville 4156404, Florida 4155751 32610
Miami 4164138, Florida 4155751 33155
Orlando 4167147, Florida 4155751 32806
St. Petersburg 4171563, Florida 4155751 33701
Atlanta 4180439, Georgia 4197000 30322
Chicago 4887398, Illinois 4896861 60611
Chicago 4887398, Illinois 4896861 60637
Indianapolis 4259418, Indiana 4921868 46202
Iowa City 4862034, Iowa 4862182 52242
Louisville 4299276, Kentucky 6254925 40202
Scarborough 4977882, Maine 4971068 04074
Boston 4930956, Massachusetts 6254926 02215
Ann Arbor 4984247, Michigan 5001836 48109
Minneapolis 5037649, Minnesota 5037779 55404
Jackson 4431410, Mississippi 4436296 39216
St Louis 4407066, Missouri 4398678 63110
Omaha 5074472, Nebraska 5073708 68198-6878
Albany 5106834, New York 5128638 12208
New York 5128581, New York 5128638 10016
New York 5128581, New York 5128638 10032
Rochester 5134086, New York 5128638 14642
Durham 4464368, North Carolina 4482348 27705
Cleveland 5150529, Ohio 5165418 44195
Portland 5746545, Oregon 5744337 97239
Austin 4671654, Texas 4736286 78723
Dallas 4684888, Texas 4736286 75390
Houston 4699066, Texas 4736286 77030
Seattle 5809844, Washington 5815135 98105
Madison 5261457, Wisconsin 5279468 53792
More Details
- NCT ID
- NCT05566795
- Status
- Recruiting
- Sponsor
- Day One Biopharmaceuticals, Inc.
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).