NCT03871257

A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma

A Phase 3 Randomized Study of Selumetinib Versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 165 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 2 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial studies if selumetinib works just as well as the standard treatment with carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to see if selumetinib is better than CV in improving vision in subjects with LGG of the optic pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that low-grade glioma tumor cells need for their growth. This results in killing tumor cells. Chemotherapy drugs, such as carboplatin and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether selumetinib works better in treating patients with NF1-associated low-grade glioma compared to standard therapy with carboplatin and vincristine.

Detailed description

PRIMARY OBJECTIVES: I. To determine whether the efficacy of treatment with selumetinib sulfate (selumetinib) as measured by event-free survival (EFS) is non-inferior to treatment with carboplatin/vincristine sulfate (vincristine) (CV) in previously untreated neurofibromatosis type 1 (NF1)-associated low-grade glioma (LGG). II. To determine whether visual acuity (VA) using Teller acuity cards (TAC), in patients with NF1-associated LGG within the optic pathway, is better in those treated with selumetinib compared to CV. SECONDARY OBJECTIVES: I. To estimate tumor response rates and overall survival (OS) in each treatment regimen in previously untreated NF1-associated LGG. II. To evaluate VA outcomes utilizing HOTV letter acuity testing in previously untreated NF1-associated LGG within the optic pathway in patients who are old enough to perform visual acuity testing utilizing HOTV (a recognition acuity measure). III. To describe the improvement in motor function as measured by the Vineland scale in patients with previously untreated NF1-associated LGG that have documented motor deficits at enrollment. IV. To prospectively evaluate and compare the quality of life among patients treated with selumetinib or CV. V. To prospectively evaluate and compare the cognitive, social, emotional, and behavioral functioning of patients with NF1-associated LGG treated with either selumetinib or CV. EXPLORATORY OBJECTIVES: I. To evaluate optical coherence tomography (OCT) measures of retinal axon and ganglion cell thickness as a marker of treatment response in previously untreated NF1-associated LGG within the optic pathway. II. To compare novel, semi-automated volumetric magnetic resonance imaging (MRI) measures to traditional measurements of treatment response (bi-dimensional MRI measurements) in NF1-associated optic pathway tumors. III. To obtain paired blood and tumor tissue to be banked for future NF1-LGG biology studies involving comprehensive molecular analysis, including but not limited to whole exome and ribonucleic acid (RNA) sequencing. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: INDUCTION: Patients receive carboplatin intravenously (IV) over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 and vincristine IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial. MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 of each cycle and vincristine IV on days 1, 8, and 15 of each cycle. Cycles repeat every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial. ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28 of each cycle. Treatment is continuous and cycles repeat every 28 days for 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial. After completion of study treatment, patients are followed up with MRIs and physical exams every 3 months for 1 year, every 6 months for 2 years, and then once yearly for up to 10 years.

Conditions

• Low Grade Glioma
• Neurofibromatosis Type 1
• Visual Pathway Glioma

Interventions

Type	Name	Description
DRUG	Carboplatin	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Selumetinib Sulfate	Given PO
DRUG	Vincristine Sulfate	Given IV or IV push

Timeline

• Start date: 2020-01-15
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2019-03-12
• Last updated: 2026-04-13

Locations

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

Regulatory

• FDA-regulated drug study