Clinical Trial: Study of Imatinib Mesylate in Neurofibromatosis Type I Patients Aged 2 to 21 With Plexiform Neurofibromas

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Study of Imatinib Mesylate in Neurofibromatosis Type I Patients Aged 2 to 21 With Plexiform Neurofibromas

Brief Summary:

This phase II trial will test the hypothesis that inhibition of c-kit signalling pathways in pediatric patients with Neurofibromatosis Type I(NF-1) and progressing plexiform neurofibroma will result in objective reduction and/or inhibition of plexiform neurofibromas progression.

This will be a Phase II study of imatinib mesylate given orally. Patients with stable or responding disease may receive the drug for a period not exceeding one year.


Detailed Summary:

Clinical objectives

  1. Demonstrate the clinical benefit of imatinib in a pediatric patient population with progressing and metabolically active plexiform neurofibromas (NF)
  2. Demonstrate the need or not to pursue treatment for more than a year in responders to imatinib

Biological studies objectives

  1. Identify biological markers of plexiform neurofibroma progression and response to treatment
  2. Identify biological markers of mast cell responses to imatinib, given that mast cells are required for tumorigenesis and are a target for imatinib

Imaging studies objectives

Using 18-Fluorodeoxyglucose-positron Emission Tomography (FDG PET/CT):

  1. Identify imaging characteristics of progressing plexiform neurofibromas
  2. Assess the role of F18-FDG PET/CT in comparison with CT/MRI to evaluate response to imatinib ¸

Pharmacological study

  1. Evaluate trough plasma levels of imatinib and its active metabolite (NDMIL N-desmethyl imatinib) achieved in this pediatric population
  2. Identify potential correlation between imatinib (and NDMI) trough levels achieved and clinical response

Sponsor: St. Justine's Hospital

Current Primary Outcome: Demonstrate the clinical benefit of imatinib in a pediatric patient population with progressing and metabolically active plexiform NFs [ Time Frame: 12 months ]

Time to tumor progression as assessed by volumetric MRI and FDG-PETScan analysis at baseline, after 3, 6, 9, and 12 months on therapy.


Original Primary Outcome: Same as current

Current Secondary Outcome: Changes in NF1 biomarkers after treatment with imatinib [ Time Frame: 12 months ]

Patients on imatinib will have blood samples and urine taken at baseline and every 3 months until treatment completion or until disease progression. Mastocyte activation biomarkers will be monitored and evaluated as potential disease state indicators.


Original Secondary Outcome: Same as current

Information By: St. Justine's Hospital

Dates:
Date Received: June 25, 2014
Date Started: June 2014
Date Completion: December 2020
Last Updated: May 5, 2017
Last Verified: May 2017