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

Titre officiel

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)

Sommaire:

Cet essai de phase III étudie si le sélumétinib fonctionne aussi bien que le traitement standard à base de carboplatine/vincristine (CV) pour les sujets atteints d’un gliome de bas grade (GBG) associé à une neurofibromatose de type 1 (NF1), et pour déterminer si le sélumétinib est meilleur que le traitement à base de CV pour améliorer la vision chez les sujets atteints d’un GBG de la voie optique (nerfs de la vision). Le sélumétinib est un médicament qui agit en bloquant certaines enzymes dont les cellules tumorales du gliome de bas grade ont besoin pour leur croissance. Cela a pour conséquence de tuer les cellules tumorales. Les médicaments utilisés en chimiothérapie, comme le carboplatine et la vincristine, agissent de différentes manières pour arrêter la croissance des cellules tumorales, soit en tuant les cellules, soit en les empêchant de se diviser ou de se propager. On ne sait pas encore si le sélumétinib est plus efficace pour traiter les patients atteints d’un gliome de bas grade associé à une NF1 que le traitement standard à base de carboplatine et de vincristine.

Description de l'essai

Primary Outcome:

  • Event-free survival (EFS)
  • Number of participants with visual acuity (VA) improvement per arm
Secondary Outcome:
  • Radiographic tumour response rate
  • Overall survival (OS)
  • Change in VA using HOTV letter acuity testing
  • Change in motor function
  • Change in quality of life (QOL)
  • Change in quality of life (QOL)
  • Change in executive function
  • Change in neurocognitive function
PRIMARY OBJECTIVES:
  • 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).
  • 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:
  • To estimate tumour response rates and overall survival (OS) in each treatment regimen in previously untreated NF1-associated LGG.
  • 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).
  • 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.
  • To prospectively evaluate and compare the quality of life among patients treated with selumetinib or CV.
  • To prospectively evaluate and compare the cognitive, social, emotional, and behavioural functioning of patients with NF1-associated LGG treated with either selumetinib or CV.
EXPLORATORY OBJECTIVES:
  • 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.
  • 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 tumours.
  • To obtain paired blood and tumour 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.

MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and vincristine IV on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity.

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. 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.

Voir cet essai sur ClinicalTrials.gov

Intéressé(e) par cet essai?

Imprimez cette page et apportez-la chez votre médecin pour discuter de votre admissibilité à cet essai et des options de traitement. Seul votre médecin peut vous recommander pour un essai clinique.

Ressources

Société canadienne du cancer

Ces ressources sont fournies en partenariat avec Société canadienne du cancer