HumRes55303
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SNCTP000004433
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BASEC2021-00344
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NCT04775485
FIREFLY-1: An open-label, multicenter Phase II study to assess the safety and efficacy of the oral pan-RAF inhibitor DAY101 in pediatric patients with RAF-altered, recurrent or progressive low-grade malignant gliomas and advanced solid tumors
Summary description of the study
This study includes a pre-screening phase, a treatment phase, a visit at the end of treatment, a safety follow-up visit after 30 days, and a long-term follow-up phase. The patient may receive DAY101 as long as the cancer does not worsen, no medically unacceptable side effects occur, and the responsible investigator believes that the health condition allows participation in this study. The estimated total duration of this study will be at least 2 years for each participant. The study ends for all participants when the last enrolled patient has completed their 2-year treatment. There are certain investigations and measures required for all patients in this study. Some are part of the routine care of cancer patients but may be performed more frequently than usual because this is a clinical study. Others serve purely scientific purposes. To participate in this study, the presence of a low-grade malignant glioma must be confirmed. This means that the diagnosis is based on cells taken from the tumor.
(BASEC)
Intervention under investigation
DAY101 in tablet form
(BASEC)
Disease under investigation
Brain tumor, pediatric low-grade malignant glioma and advanced solid tumors
(BASEC)
Criteria for participation in trial
Patients aged 6 months to 25 years with a recurrent or progressive LGG with documented known activating BRAF alteration, demonstrated using molecular assays as routinely performed in CLIA or other appropriately certified laboratories. Confirmation of the histopathological diagnosis of an LGG, i.e., either the original diagnosis or a recurrence/progression. Patients must have received at least one line of systemic therapy, and there must be documented radiological evidence of disease progression for the patient in question. (BASEC)
Exclusion criteria
The patient's tumor has other known activating molecular alterations (e.g., histone mutation, IDH1/2 mutations, FGFR mutations or fusions, MYBL alterations, NF1 mutations (somatic or germline)). The patient exhibits symptoms of clinical progression without radiographically detectable recurrent or progressive disease. Known or suspected diagnosis of Neurofibromatosis Type 1 (NF-1) by genetic testing or according to current diagnostic criteria. (BASEC)
Patients aged 6 months to 25 years with a recurrent or progressive LGG with documented known activating BRAF alteration, demonstrated using molecular assays as routinely performed in CLIA or other appropriately certified laboratories. Confirmation of the histopathological diagnosis of an LGG, i.e., either the original diagnosis or a recurrence/progression. Patients must have received at least one line of systemic therapy, and there must be documented radiological evidence of disease progression for the patient in question. (BASEC)
Exclusion criteria
The patient's tumor has other known activating molecular alterations (e.g., histone mutation, IDH1/2 mutations, FGFR mutations or fusions, MYBL alterations, NF1 mutations (somatic or germline)). The patient exhibits symptoms of clinical progression without radiographically detectable recurrent or progressive disease. Known or suspected diagnosis of Neurofibromatosis Type 1 (NF-1) by genetic testing or according to current diagnostic criteria. (BASEC)
Trial sites
Zurich
(BASEC)
Australia, Canada, Denmark, Germany, Israel, Korea, Republic of, Netherlands, Singapore, Switzerland, United Kingdom, United States (ICTRP)
Sponsor
Iqvia RDS AG, Kirschgartenstrasse 12/14, 4051 Basel
(BASEC)
Contact
Contact Person Switzerland
Dr. med. Nicolas Gerber
+41 44 266 7455
nicolas.gerber@clutterkispi.uzh.chUniversitäts-Kinderspital, Lenggstrasse 30 CH-8008 Zürich
(BASEC)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
01.06.2021
(BASEC)
ICTRP Trial ID
NCT04775485 (ICTRP)
Official title (approved by ethics committee)
FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients with RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors (BASEC)
Academic title
FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors (ICTRP)
Public title
A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors (ICTRP)
Disease under investigation
Low-grade Glioma;Advanced Solid Tumor (ICTRP)
Intervention under investigation
Drug: DAY101 (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Gender: All
Maximum age: 25 Years
Minimum age: 6 Months
Inclusion Criteria:
- Age 6 months to 25 years with:
1. Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF
alteration
2. Arm 3: locally advanced or metastatic solid tumor with documented known or
expected to be activating RAF fusion
- Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating
BRAF alteration
- Must have received at least one line of systemic therapy and have evidence of
radiographic progression
- Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1
(Arm 3) criteria
Exclusion Criteria:
- Patient's tumor has additional previously-known activating molecular alterations
- Patient has symptoms of clinical progression in the absence of radiographic
progression
- Known or suspected diagnosis of neurofibromatosis type 1 (NF-1)
- Other inclusion/exclusion criteria as stipulated by protocol may apply
(ICTRP)
not available
Primary and secondary end points
Arm 1: Overall response rate (ORR) by independent radiology review committee (IRC) based on RANO criteria;Arm 2: Assess the safety and tolerability of DAY101;Arm 3: Overall response rate (ORR) by independent radiology review committee (IRC) based on RECIST v1.1 criteria (ICTRP)
Relationship between pharmacokinetics (PK) and drug effects;Effect on electrocardiogram (ECG) and QT interval corrected for heart rate by Fridericia's formula (QTcF) prolongation;ORR by Investigator;Evaluate the concordance of prior local laboratory BRAF molecular profiling with a central BRAF alteration assay being evaluated by the Sponsor;Arm 1: Evaluate visual acuity (VA) outcomes compared with baseline;Arms 1 & 2: ORR by IRC and Investigator using RAPNO criteria;Arms 1 & 2: Progression free survival (PFS) using RANO and RAPNO criteria by 1) an IRC and 2) the treating Investigator (RANO only);Arms 1 & 2: Duration of response (DOR) with best overall response of CR or PR using RANO and RAPNO criteria by 1) an IRC and 2) the treating Investigator (RANO only);Arms 1 & 2: Time to response following initiation of DAY101;Arms 1 & 2: Clinical benefit rate based on the proportion of patients with best overall response using RANO or RAPNO criteria;Arms 1 & 3: Assess the safety and tolerability of DAY101;Arm 3: Duration of response (DOR) with best overall response of CR or PR using RECIST v1.1 criteria by 1) an IRC and 2) the treating Investigator;Arm 3: Time to response following initiation of DAY101;Arm 3: Clinical benefit rate based on the proportion of patients with best overall response using RECIST v1.1 criteria (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
Pacific Pediatric Neuro-Oncology Consortium (ICTRP)
Additional contacts
Day One Biopharmaceuticals;braintumorresearch@childrensnational.org, firefly-1@dayonebio.com, 650-484-0899;202-476-5000 (ICTRP)
Secondary trial IDs
DAY101-001/PNOC026 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT04775485 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available