LOGGIC/FIREFLY-2: A randomized, international, multicenter phase III study of DAY101 monotherapy compared to standard chemotherapy in patients with pediatric low-grade glioma with an activating RAF alteration requiring systemic first-line therapy.
Summary description of the study
This study aims to treat a brain tumor referred to as pediatric low-grade glioma (pLGG), which has an anomaly in a protein called RAF (summarized as RAF alteration), with the investigational drug Tovorafenib (DAY101) compared to an approved chemotherapy, i.e., it will be investigated whether Tovorafenib is safe and well-tolerated and how well it works compared to standard chemotherapy (SC). Patients participating in this study will receive Tovorafenib (the investigational drug) or SC. The probability that a patient receives Tovorafenib or SC is 50:50 (like flipping a coin). The SC includes several options of Vincristine/Carboplatin or Vinblastine, which are used in standard medical practice for the treatment of pLGG. The physician will decide which chemotherapy the patient will receive if assigned to the SC group. Approximately 400 patients under 25 years of age will participate in this study across various countries. Participation in the study will last about 5 years and will include a screening visit and further clinic visits (every 4-6 weeks during the 1 to 2-year treatment phase and every 2-3 months for tumor monitoring after treatment). Patients in the SC group will come to the clinic more frequently for their treatment than patients in the Tovorafenib group. Tovorafenib is offered as a tablet or powder for reconstitution.
(BASEC)
Intervention under investigation
If a patient is interested in participating in this study, he and/or his parents will first receive a patient information and consent form, which details all aspects of the study. The information contained therein and any further questions will be discussed in an informational interview with an investigator. Only after signing the consent form can the screening phase begin.
Screening: Within 28 days of signing the consent form, the investigator will assess whether participation in the study is appropriate for the patient based on various measures (including tumor imaging via MRI).
For patients included in Arm 1 (Tovorafenib), the treatment period consists of "cycles" of 28 days, meaning that the treatment cycles will be repeated every 28 days and DAY101 will be administered on days 1, 8, 15, and 22 of each 28-day cycle. The once-weekly dose can be taken either as a tablet or as a powder dissolved in water.
For patients in Arm 2 (SC), the treatment cycles are specific to the chemotherapy they receive (normally 4-6 weeks). The total duration of treatment is 60-81 weeks (approximately 13-18 months), depending on which chemotherapy is administered. Chemotherapy is usually given by infusion into a vein.
Participation in this study includes the collection of blood and urine samples, an electrocardiogram (ECG), an echocardiogram (ECHO), eye examinations, X-rays, and MRIs.
Benefit: Treatment with Tovorafenib or SC may improve, worsen, or have no impact on the patient's health. A potential benefit cannot be guaranteed.
Risk and burden: There is a risk of side effects from both taking Tovorafenib and receiving SC (some of which may be severe). Patients and/or their parents receive detailed information about possible side effects of each treatment in the patient information before deciding whether to participate in this study. Additionally, there may be risks associated with study-related procedures such as blood draws or imaging studies.
(BASEC)
Disease under investigation
Pediatric low-grade glioma with activating RAF alteration
(BASEC)
-Patient must be younger than 25 years old with a diagnosis of low-grade glioma with known activating RAF change -At least one measurable lesion according to a set of standardized assessment criteria (so-called RANO criteria) - Fulfillment of the indication for systemic first-line therapy (BASEC)
Exclusion criteria
- The patient has any of the following tumor tissue findings: a) Schwannoma b) Subependymal giant cell astrocytoma (tuberous sclerosis) c) Diffuse intrinsic pontine glioma, even if histologically diagnosed as WHO grade I-II -The patient's tumor has additional activating molecular alterations. -Known or suspected diagnosis of neurofibromatosis type 1 or 2 (NF1/NF-2). - Previous or ongoing non-surgical cancer therapy for this indication (e.g. chemotherapy, oral/IV targeted therapy) including radiation. (BASEC)
Trial sites
Lausanne, Zurich
(BASEC)
Sponsor
Day One Biopharmaceuticals, Inc. (Day One) PRA Switzerland AG
(BASEC)
Contact
Contact Person Switzerland
Prof. Dr. med. Ana Guerreiro Stuecklin
+41 44 266 74 55
ana.stuecklin@clutterkispi.uzh.chUniversitäts-Kinderspital Zürich
(BASEC)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
14.03.2023
(BASEC)
ICTRP Trial ID
NCT05566795 (ICTRP)
Official title (approved by ethics committee)
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 (BASEC)
Academic 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 (ICTRP)
Public title
DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2) (ICTRP)
Disease under investigation
Low-grade GliomaRapidly Accelerated Fibrosarcoma (RAF) Altered GliomaPediatric Low-grade Glioma (ICTRP)
Intervention under investigation
Drug: TovorafenibDrug: Chemotherapeutic Agent (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion 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. (ICTRP)
not available
Primary and secondary end points
Objective response rate (ORR) of tovorafenib monotherapy versus SoC chemotherapy (ICTRP)
Progression-free survival (PFS) of tovorafenib monotherapy versus SoC chemotherapy;Event-free survival (EFS) of tovorafenib monotherapy versus SoC chemotherapy;Overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy;Number of participants with any treatment-emergent adverse events, and Serious adverse events;. Number of participants with clinically significant vital signs and laboratory abnormalities findings;Change from baseline in Adaptive Behavior Composite Score (ABS) of tovorafenib monotherapy versus SoC chemotherapy;Change from baseline in the Motor Skills Domain Score of tovorafenib monotherapy versus SoC chemotherapy;Change from baseline in the Daily Living Domain Score of tovorafenib monotherapy versus SoC chemotherapy;Change from baseline in the Communication Domain Score of tovorafenib monotherapy versus SoC chemotherapy;Change from baseline in the Socialization Domain Score of tovorafenib monotherapy versus SoC chemotherapy;Change in age-adjusted visual acuity (VA) of tovorafenib monotherapy versus SoC chemotherapy in optic pathway glioma (OPG) participants aged < 3 years;Change in best corrected visual acuity of tovorafenib monotherapy versus SoC chemotherapy in OPG participants aged = 3 years;Visual progression-free survival (v-PFS) of tovorafenib monotherapy versus SoC chemotherapy;ORR of tovorafenib monotherapy versus SoC chemotherapy;Clinical bene?t rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy;Time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy;PFS of tovorafenib monotherapy versus SoC chemotherapy;EFS of tovorafenib monotherapy versus SoC chemotherapy;Duration of response (DOR) of tovorafenib monotherapy versus SoC chemotherapy;Change from Baseline in health-related quality of life (HRQoL) total score of tovorafenib monotherapy versus SoC chemotherapy (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
SIOPe Brain Tumor Group LOGGIC Consortium (ICTRP)
Additional contacts
Day One Clinical Trials Information, clinicaltrials@dayonebio.com, 650-484-0899 (ICTRP)
Secondary trial IDs
2022-001363-27, DAY101-002 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT05566795 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available