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A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma (FIREFLY-1)

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ClinicalTrials.gov Identifier: NCT04775485
Recruitment Status : Recruiting
First Posted : March 1, 2021
Last Update Posted : August 12, 2021
Sponsor:
Collaborator:
Pacific Pediatric Neuro-Oncology Consortium
Information provided by (Responsible Party):
DOT Therapeutics-1 Inc. ( Day One Biopharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE February 3, 2021
First Posted Date  ICMJE March 1, 2021
Last Update Posted Date August 12, 2021
Actual Study Start Date  ICMJE March 17, 2021
Estimated Primary Completion Date March 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2021)
Overall response rate (ORR) by independent radiology review committee (IRC) based on RANO criteria [ Time Frame: Up to 48 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2021)
  • Assess the safety and tolerability of DAY101 [ Time Frame: Up to 48 months ]
    Type, frequency, and severity of treatment-emergent adverse events and laboratory abnormalities
  • Relationship between pharmacokinetics (PK) and drug effects [ Time Frame: Up to 48 months ]
    Pharmacokinetic profile of DAY101 (e.g., area under the concentration-time curve [AUC], Cmin, etc.)
  • Effect on electrocardiogram (ECG) and QT interval corrected for heart rate by Fridericia's formula (QTcF) prolongation [ Time Frame: Up to 48 months ]
    Change from baseline QT interval corrected for HR by Fridericia's formula (ΔQTcF); change from baseline PR interval (ΔPR); change from baseline QRS interval (ΔQRS); change from baseline heart rate (ΔHR); ECG waveform morphology
  • ORR by Investigator using RANO criteria [ Time Frame: Up to 48 months ]
    Measured by the proportion of patients with best overall confirmed response of CR or PR by RANO criteria
  • ORR by IRC and Investigator using RAPNO criteria [ Time Frame: Up to 48 months ]
    Measured by the proportion of patients with best overall confirmed response of CR or PR by RAPNO-LGG criteria
  • Progression free survival (PFS) by IRC and Investigator using RANO and RAPNO criteria [ Time Frame: Up to 48 months ]
    Measured by the time following initiation of DAY101 to progression or death in patients treated with DAY101
  • Duration of response (DOR) with best overall response of CR or PR using RANO and RAPNO criteria [ Time Frame: Up to 48 months ]
    Measured by the length of response in patients with best overall confirmed response of CR or PR by RANO criteria
  • Time to response following initiation of DAY101 [ Time Frame: Up to 48 months ]
    Measured by the time to first response following initiation of DAY101 in patients with best overall confirmed response of CR or PR by RANO criteria
  • Clinical benefit rate based on the proportion of patients with best overall response [ Time Frame: Up to 48 months ]
    Measured on the proportion of patients with best overall response of CR, PR, or SD lasting 12 months or more following initiation of DAY101
  • Evaluate visual acuity (VA) outcomes compared with baseline [ Time Frame: Up to 48 months ]
    Measured by Teller Acuity Cards® II
  • Evaluate the concordance of prior local laboratory BRAF molecular profiling with a central BRAF alteration assay being evaluated by the Sponsor [ Time Frame: Up to 48 months ]
    Molecular analysis of cells obtained from archival tissue
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 25, 2021)
  • Compare the response and time to progression following initiation of DAY101 to that of the prior line of systemic therapy [ Time Frame: Up to 48 months ]
    Measured by the proportion of patients with best overall confirmed response of CR or PR and time to response by RANO criteria based on the prior line of therapy
  • Characterize changes in total tumor volume following treatment with DAY101 by magnetic resonance imaging (MRI) volumetric image analysis [ Time Frame: Up to 48 months ]
    Measured by determining tumor volume and volume changes based on MRI scan data
  • Characterize changes in apparent diffusion coefficients following treatment with DAY101 using diffusion-weighted imaging analysis [ Time Frame: Up to 48 months ]
    Measured by diffusion-weighted imaging based on MRI scan data
  • Evaluate changes from baseline in quality-of-life and health utilities measures using the Pediatrics Quality of Life™-Core Module (PedsQL-Core) and Patient-Reported Outcomes Measurement Information System (PROMIS®) assessment [ Time Frame: Up to 48 months ]
    Measured by changes from baseline in quality-of-life and health utilities measures using the PedsQL-Core and PROMIS assessment
  • Describe the improvement in motor function compared with baseline [ Time Frame: Up to 48 months ]
    Measured by changes in the Vineland 3 Adaptive Behavior Scales
  • Determine the durability of response following discontinuation of DAY101 for patients with a radiographic response to DAY101 (CR or PR as based on RANO and RAPNO criteria) as determined by 1) an IRC and 2) the treating Investigator [ Time Frame: Up to 48 months ]
    Measured by the proportion of patients with best overall confirmed response of CR or PR who enter a drug holiday period and time to progression as determined by RANO or clinical criteria
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma
Official Title  ICMJE 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 BRAF-Altered, Recurrent or Progressive Low-Grade Glioma
Brief Summary FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma harboring a known BRAF alteration.
Detailed Description

Approximately 60 pediatric patients will be treated with DAY101, an oral pan-RAF inhibitor, for a planned period of 26 cycles will be treated with DAY101 for a planned period of 26 cycles (approximately 24 months).

DAY101 will be administered at the recommended Phase 2 dose (RP2D) of 420 mg/m2 (not to exceed 600 mg) orally once weekly (QW) for each 28-day treatment cycle.

Treatment cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients will undergo radiographic evaluation of their disease at the end of every third cycle. Patients will continue on DAY101 until radiographic evidence of disease progression by RANO criteria as determined by treating investigator, unacceptable toxicity, patient withdrawal of consent, or death.

Patients who have radiographic evidence of disease progression may be allowed to continue DAY101 if, in the opinion of the investigator and approval by the Sponsor, the patient is deriving clinical benefit from continuing study treatment. Disease assessments for patients being treated beyond progression should continue as per regular schedule.

DAY101 is an oral pan-RAF inhibitor administered as an oral tablet at 420 mg/m2 (not to exceed 600 mg).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Low-grade Glioma
Intervention  ICMJE Drug: DAY101
DAY101 is an oral pan-RAF inhibitor provided as a white to off-white crystalline powder as an immediate-release tablet in 2 strengths, 20 mg and 100 mg.
Study Arms  ICMJE Experimental: Single Arm
DAY101, an oral pan-RAF inhibitor in immediate-release tablet form in 2 strengths, 20 mg and 100 mg.
Intervention: Drug: DAY101
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 25, 2021)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2024
Estimated Primary Completion Date March 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 6 months to 25 years with a relapsed or progressive LGG with known activating BRAF alteration
  • 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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Day One Biopharmaceuticals 650-484-0899 firefly-1@dayonebio.com
Listed Location Countries  ICMJE Australia,   Canada,   Korea, Republic of,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04775485
Other Study ID Numbers  ICMJE DAY101-001/PNOC026
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party DOT Therapeutics-1 Inc. ( Day One Biopharmaceuticals, Inc. )
Study Sponsor  ICMJE Day One Biopharmaceuticals, Inc.
Collaborators  ICMJE Pacific Pediatric Neuro-Oncology Consortium
Investigators  ICMJE Not Provided
PRS Account DOT Therapeutics-1 Inc.
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP