NCT04166409

A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma

A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine Versus Selumetinib (NSC# 748727) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) Not Associated With BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 170 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 2 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial compares the effect of selumetinib versus the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG. Another goal of this study is to compare the effects of selumetinib versus CV in subjects with LGG to find out which is better. Additionally, this trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it.

Detailed description

PRIMARY OBJECTIVE: I. To demonstrate that the efficacy of treatment with selumetinib as measured by event-free survival (EFS) is non-inferior compared to treatment with carboplatin/vincristine (CV) in previously-untreated low-grade glioma (LGG) not associated with BRAFV600E mutations or systemic neurofibromatosis type 1 (NF1). SECONDARY OBJECTIVES: I. To estimate tumor response rates to each regimen of chemotherapy. II. To evaluate visual acuity (VA) outcomes utilizing Teller Acuity Cards (TAC) and HOTV letter acuity testing in previously-untreated optic pathway gliomas (OPGs). III. To describe the improvement in motor function as measured by the Vineland Scale in children with previously-untreated LGG that have motor deficits at enrollment. IV. To estimate the difference in EFS and tumor response rate between BRAF rearranged and non-BRAF rearranged patients treated on each chemotherapy regimen. V. To prospectively evaluate the quality of life of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib. VI. To prospectively evaluate the cognitive, social, emotional, and behavioral functioning of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib. EXPLORATORY OBJECTIVE: I. To obtain paired blood and tumor specimens for future biology studies as well as data from Molecular Characterization Initiative (MCI) testing, to correlate genomic drivers to efficacy outcomes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: INDUCTION: Patients receive vincristine sulfate intravenously (IV) on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64, and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and magnetic resonance imaging (MRI) throughout the trial. MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and MRI throughout the trial. ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) at baseline and undergo collection of blood and MRI throughout the trial. After completion of study treatment, patients are followed up every 3 months for year 1, every 6 months for years 2-3, and then annually for years 4-10.

Conditions

• Low Grade Astrocytoma
• Low Grade Glioma
• Metastatic Low Grade Astrocytoma
• Metastatic Low Grade Glioma
• WHO Grade 1 Glioma
• WHO Grade 2 Glioma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Carboplatin	Given IV
PROCEDURE	Echocardiography Test	Undergo ECHO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Selumetinib Sulfate	Given PO
DRUG	Vincristine Sulfate	Given IV

Timeline

• Start date: 2020-01-31
• Primary completion: 2030-12-31
• Completion: 2030-12-31
• First posted: 2019-11-18
• Last updated: 2026-04-14

Locations

132 sites across 3 countries: United States, Canada, Puerto Rico

Regulatory

• FDA-regulated drug study