NCT06381570

Pilot Study of Vinblastine and Tovorafenib in Pediatric Patients With Recurrent/Progressive RAF Altered Low Grade Gliomas

VICTORY: A Pilot Study to Investigate Safety and Efficacy of Weekly Combination of Intravenous Vinblastine With Oral Type II RAF Inhibitor Tovorafenib in Pediatric Patients With Recurrent/Progressive RAF Altered Low Grade Gliomas

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 57 (estimated)
• Sponsor: Daniel Morgenstern · Academic / Other
• Sex: All
• Age: 0 Weeks – 25 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

Phase A (Feasibility Phase) A feasibility phase will be conducted to establish the maximum tolerated dose (MTD/RP2D) of the combination of vinblastine + tovorafenib using the Rolling 6 design. Patients will receive vinblastine and tovorafenib on Days 1, 8, 15, 22 of each cycle for a total duration of 17 cycles followed by 7 additional cycles of tovorafenib alone. One cycle of protocol therapy is 28 days. Treatment cycles will repeat every 28 days for a total of 24 cycles in the absence of disease progression or unacceptable toxicity. Patients will undergo radiographic evaluation of their disease at the end of every third cycle, starting with the end of Cycle 3. The RP2D of tovorafenib of 420 mg/m2 once weekly (not exceeding 600 mg) in combination with vinblastine (4mg/m2) will be used as the starting dose and will be de-escalated/escalated as per Table 4. Dose of tovorafenib will not be escalated further. Patients will be treated on protocol therapy for a total of 24 cycles, the vinblastine and tovorafenib for a total duration of 17 cycles followed by 7 additional cycles of alone tovorafenib, unless disease progression, unacceptable toxicity occurs, or withdrawal from the study occurs. Missed doses of either vinblastine or tovorafenib will not be made up. Phase B (Expansion/Efficacy Phase) Once the MTD/RP2D of the combination, vinblastine + tovorafenib has been established, the expansion/efficacy phase will be initiated at the dose determined in Phase A. Patient will receive vinblastine and tovorafenib weekly on Days 1, 8, 15, 22 of each cycle at dose determined in Phase A for a total duration of 17 cycles followed by 7 additional cycles of tovorafenib alone. One cycle of protocol therapy is 28 days. 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, starting with the end of Cycle 3. Patients will be treated on protocol therapy for a total of 24 cycles, the vinblastine and tovorafenib for a total duration of 17 cycles followed by 7 additional cycles of alone tovorafenib, unless disease progression or unacceptable toxicity occurs, unless disease progression, unacceptable toxicity or withdrawal from study occurs. Missed doses of either vinblastine or tovorafenib will not be made up.

Conditions

• Low-grade Glioma

Interventions

Type	Name	Description
DRUG	Tovorafenib	Tovorafenib for oral dosing is provided as an immediate-release tablet in 100 mg strength. The 100 mg tablets are red to yellowish red oval tablets. All products are labeled tovorafenib. In addition, tovorafenib is provided as a powder for reconstitution (PfR) in bottles (430mg per bottle to deliver 300 mg dose). Upon reconstitution with water, the concentration is 25 mg/mL. Vinblastine is administered by intravenous route as IV push, sites to follow local administration guidelines, once weekly (central line, but peripheral line is also permitted)
DRUG	Vinblastine	vinblastine in combination with tovorafenib

Timeline

• Start date: 2024-03-21
• Primary completion: 2027-03-21
• Completion: 2029-03-21
• First posted: 2024-04-24
• Last updated: 2025-05-15

Locations

1 site across 1 country: Canada