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 or IV push over 1 minute 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 during screening and on study.
MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and
vincristine IV or IV push over 1 minute on days 1, 8, and 15. Treatment repeats every 6 weeks
for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also
undergo MRI on study and during follow-up.
ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28.
Treatment is continuous and repeats 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.