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

Official Title

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)

Summary:

This trial studies how well selumetinib works in treating patients with low-grade glioma. Selumetinib is a drug that works by blocking a protein (a basic building block of the human body) that lets tumour cells grow without stopping. Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop the growth of tumour cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial studies if selumetinib works as well as carboplatin and vincristine for getting rid of or shrinking low-grade gliomas and stopping them from coming back.

Trial Description

Primary Outcome:

  • Event-free survival (EFS)
Secondary Outcome:
  • Radiographic tumour response rate
  • Overall survival (OS)
  • Proportion of patients who experience an improvement in visual acuity (VA)
  • Motor function assessment
  • Change in parent and patient-reported quality of life (QOL) over time

PRIMARY OBJECTIVE:

  • 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:

  • To estimate tumour response rates to each regimen of chemotherapy.
  • To evaluate visual acuity (VA) outcomes utilizing Teller Acuity Cards (TAC) and HOTV letter acuity testing in previously-untreated optic pathway gliomas (OPGs).
  • 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.
  • To estimate the difference in EFS and tumour response rate between BRAF rearranged and non-BRAF rearranged patients treated on each chemotherapy regimen.
  • To prospectively evaluate the quality of life of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib.
  • To prospectively evaluate the cognitive, social, emotional, and behavioural functioning of children with LGG not associated with BRAFV600E or systemic NF1 treated with either CV or selumetinib.

EXPLORATORY OBJECTIVE:

  • To obtain paired blood and tumour specimens for future biology studies, including studies to correlate genomic drivers to response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: INDUCTION: Patients receive vincristine intravenously (IV) over 1 minute 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.

MAINTENANCE: Patients receive vincristine IV over 1 minute on days 1, 8, and 15, and carboplatin IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive selumetinib orally (PO) twice daily (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 then annually for years 4-10.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society