Actively Recruiting
Pilot Study of Vinblastine and Tovorafenib in Pediatric Patients With Recurrent/Progressive RAF Altered Low Grade Gliomas
Led by Daniel Morgenstern · Updated on 2025-05-15
57
Participants Needed
1
Research Sites
260 weeks
Total Duration
On this page
Sponsors
D
Daniel Morgenstern
Lead Sponsor
T
The Hospital for Sick Children
Collaborating Sponsor
AI-Summary
What this Trial Is About
This is a Pilot, multicenter, open-label study of patients less than or equal to 25 years, with recurrent or progressive LGG harboring a CRAF or BRAF alteration, including BRAF V600 mutations and KIAA1549: BRAF fusions. Patients with BRAF or CRAF alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories. The study will be conducted in two sequential phases: Phase A: A Feasibility (combination dose finding) phase, followed by Phase B: An Efficacy phase. The maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of the combination as determined in Phase A would be the dose used in Phase B. The patients on Phase A who were below the MTD/RP2D would be eligible for intra-patient dose escalation to MTD/RP2D subject to criteria outlined later
CONDITIONS
Official Title
Pilot Study of Vinblastine and Tovorafenib in Pediatric Patients With Recurrent/Progressive RAF Altered Low Grade Gliomas
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must be 25 years old or younger at enrollment.
- Diagnosis of progressive or recurrent low-grade glioma with confirmed BRAF or CRAF alteration.
- Pathological confirmation of low-grade glioma with BRAF or CRAF alteration.
- At least one measurable tumor lesion.
- Eligible tumor types include WHO grade I and II low-grade gliomas except subependymal giant cell astrocytoma.
- Prior treatment with at least one systemic therapy such as vinca alkaloid, carboplatin, MEK inhibitor, or BRAF inhibitor.
- Recovery from acute side effects of prior treatments.
- Adequate bone marrow, liver, kidney, thyroid, cardiac, and central nervous system function.
- Stable neurologic status and seizure control.
- Ability to comply with treatment and clinic visits.
- Availability of archival or fresh tumor tissue sample.
- Baseline eye exam and MRI within 28 days before enrollment.
- Willingness to use effective birth control during and after treatment.
- Ability to swallow tablets or receive medication via gastric tube.
- Ability to start treatment within 14 working days of screening.
- Informed consent and assent as applicable.
You will not qualify if you...
- Tumors with other known activating molecular alterations besides BRAF or CRAF.
- Diagnosis of neurofibromatosis Type 1.
- History of major diseases interfering with safe participation.
- History or current evidence of central serous retinopathy, retinal vein occlusion, or ophthalmopathy posing risk.
- Major surgery within 14 days before enrollment (except certain procedures).
- Significant active cardiovascular disease or recent heart events.
- Use of strong CYP2C8 or CYP3A4 inhibitors/inducers or narrow therapeutic index BCRP substrates within 14 days before therapy.
- Participation in other investigational treatment studies.
- Active systemic infections.
- Severe nausea, vomiting, or malabsorption affecting drug absorption.
- High-grade creatine phosphokinase elevation.
- Neurologic instability despite treatment.
- Pregnancy or breastfeeding.
- History of severe drug reactions like DRESS or Stevens Johnson syndrome.
- Hypersensitivity to study drugs or their components.
- Other conditions making the patient unsuitable as judged by the investigator.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Actively Recruiting
Research Team
N
Nirav Thacker
CONTACT
A
Aiman Siddiqi
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here