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
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.
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.
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
V. To examine the vision outcomes among patients with optic pathway gliomas (OPGs) treated
with selumetinib + vinblastine and single-agent selumetinib.
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
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.
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.
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.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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