Trametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway.

Sponsor
St. Justine's Hospital
Study ID
NCT03363217
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Central Nervous System Glioma
  • Low-grade Glioma
  • Plexiform Neurofibroma

Eligibility Criteria

Sex
ALL
Age
1 Month - 25 Years
Healthy Volunteers
Not accepted

Interventions

  • Trametinib — DRUG
    Daily administration of oral trametinib at a unique dose of 0.025 mg/kg.

Study Details

This is a phase 2, open-label, interventional clinical trial that will study the response rate of pediatric glioma and plexiform neurofibroma (PN) to oral administration of trametinib. Patients meeting all inclusion criteria for a given study group will receive the study medication at a daily dose of 0.025 mg/kg up to a total of 18 cycles, in 28-day cycles. A total of 150 patients will be recruited as part of this clinical study. Patients aged between 1 month (corrected age) and 25 years old will be eligible, in order to include a maximum of patients affected by low-grade glioma (LGG) and PN. This study includes four groups: patients with neurofibromatosis type 1 (NF1) and LGG, NF1 patients with PN, patients with LGG with a B-Raf Serine/Threonine-protein Kinase/Proto-oncogene Encoding B-Raf (BRAF) fusion and patients with glioma of any grade with activation of the Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinases (MAPK/ERK) pathway. All patients except patients with PN must have failed at least one line of treatment. The study will also explore the molecular mechanisms behind tumor development, progression and resistance to treatment. Furthermore, this study will also explore important aspects for patients with brain tumors by including assessment of quality of life and neuropsychological evaluation.

Key Dates

Start date
Aug 16, 2018
Status verified
Apr 2026
Primary completion
Mar 1, 2027
Completion
Mar 1, 2027

Study Design

Enrollment
114 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Neurofibromatosis Type 1 (NF1) with low-grade glioma
    Patients presenting with Neurofibromatosis Type 1 (NF1) and a progressing/refractory low-grade glioma.
  • Experimental: Neurofibromatosis Type 1 (NF1) with Plexiform Neurofibroma
    Patients presenting with Neurofibromatosis Type 1 (NF1) and a plexiform neurofibroma
  • Experimental: Progressing/refractory low grade-glioma, KIAA1549-BRAF fusion
    Patients presenting with a progressing/refractory low-grade glioma with a KIAA1549-BRAF fusion.
  • Experimental: Progressing/Refractory central nervous system (CNS) glioma.
    Patients presenting with a progressing/refractory central nervous system glioma with an activation of the MAPK/ERK pathway who do not meet criteria for inclusion in other study groups.

Primary Outcome Measure

Objective Response Rate [ Time Frame: From date of treatment start until the date of first documented progression, up to completion of treatment (504 treatment days). ]

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