NCT04576117

A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma

A Phase 3 Study of Selumetinib (NSC# 748727) or Selumetinib in Combination With Vinblastine for Non-NF1, Non-TSC Patients With Recurrent or Progressive Low-Grade Gliomas (LGGs) Lacking BRAFV600E or IDH1 Mutations

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 2 Years – 25 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial investigates the best dose of vinblastine in combination with selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib alone in treating children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment (recurrent) or does not respond to therapy (progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill cancer cells. Giving selumetinib in combination with vinblastine may work better than selumetinib alone in treating recurrent or progressive low-grade glioma.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of selumetinib sulfate (selumetinib) + vinblastine sulfate (vinblastine) for children with progressive or recurrent low-grade gliomas (LGGs). II. To determine if selumetinib + vinblastine will lead to improved event-free survival (EFS) outcome compared with selumetinib alone for children with progressive or recurrent LGGs. SECONDARY OBJECTIVES: I. To estimate the objective response rates and overall survival associated with treatment with selumetinib + vinblastine versus single-agent selumetinib. II. To estimate the difference in EFS and response rate between patients with BRAF rearranged LGG and patients with non-BRAF rearranged LGG after treatment with selumetinib + vinblastine versus single-agent selumetinib. III. To evaluate toxicities associated with selumetinib + vinblastine and single-agent selumetinib for children with progressive or recurrent LGGs. IV. To compare the quality of life among patients treated with selumetinib + vinblastine and single-agent selumetinib. V. To examine the vision outcomes among patients with optic pathway gliomas (OPGs) treated with selumetinib + vinblastine and single-agent selumetinib. EXPLORATORY OBJECTIVE: I. To obtain paired blood and tumor specimens for future biology studies, including studies to correlate genomic drivers to response. OUTLINE: This is a dose-escalation feasibility study of vinblastine sulfate in combination with selumetinib, followed by a randomized efficacy study. Patients in the feasibility study are assigned to Arm I, while patients in the efficacy study are randomized to Arm I or Arm II. ARM I: Patients receive vinblastine sulfate intravenously (IV) over 1 minute or IV infusion on days 1, 8, 15, and 22 and selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days. Patients receive selumetinib and vinblastine for a total duration of 17 cycles followed by 10 additional cycles of selumetinib alone in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection during screening and on study. ARM II: Patients receive selumetinib sulfate PO BID on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial. Patients also undergo blood sample collection during screening and on study. After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and annually for years 4-5.

Conditions

• Recurrent Low Grade Astrocytoma
• Recurrent WHO Grade 2 Glioma
• Refractory Low Grade Astrocytoma
• Refractory Low Grade Glioma
• Refractory WHO Grade 1 Glioma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Selumetinib Sulfate	Given PO
DRUG	Vinblastine Sulfate	Given IV

Timeline

• Start date: 2021-02-16
• Primary completion: 2026-12-30
• Completion: 2026-12-30
• First posted: 2020-10-06
• Last updated: 2026-04-13

Locations

101 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study