Clinical Trial: Efficacy and Safety of RAD001 in Treating Plexiform Neurofibromas (PN) Associated With Neurofibromatosis (NF1)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase II Study of RAD001 in the Treatment of Patients With Plexiform Neurofibromas (PN) Associated With Neurofibromatosis Type 1 (NF1)

Brief Summary:

This study was to evaluate the antitumor activity and safety of RAD001 in patients with Plexiform neurofibromas (PN) associated with Neurofibromatosis Type 1 (NF1).

The aim of the study was to :

  1. determine whether RAD001, administrated orally daily on a continuous dosing schedule might:

    1. Increases time to disease progression (TTP) based on volumetric MRI measurements in children and adults with NF1 in inoperable documented progressive PN (stratum 1).
    2. Results in objective radiographic responses based on volumetric MRI measurements in children and adults with NF1 and inoperable PN in the absence of documented radiographic progression at the trail entry (stratum
  2. To evaluate the tolerability and toxicity of chronic RAD001 administration in this patient population as assessed by the NCI Common Toxicity Criteria, version 4.0.

Detailed Summary:

Approximately 20 patients were to be enrolled to receive everolimus in an open label manner. A total of 9 patients were enrolled to either Stratum 1 or Stratum 2.

The study was open for enrollment up to 2 years. Because the target enrollment was not achieved in this period, study was terminated with less patient than planned.


Sponsor: Novartis Pharmaceuticals

Current Primary Outcome:

  • Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only) [ Time Frame: Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days) ]
    This endpoint was planned to be analyzed for only Stratum 1 patients. Progression of disease defined as a ≥ 20% increase in the volume (by volumetric MRI) of at least one of the index plexiform neurofibromas (PN) compared to the pretreatment volume measured prior to the start of the current treatment phase.
  • Number of Patients With Objective Radiographic Responses Based on Volumetric MRI Measurements (In Stratum 2 Only) [ Time Frame: Screening, after course #6, then every 6 months and end of treatment(1 course=28days) ]

    Response was assessed at the time that a follow up volumetric MRI scan is performed (after course 6 and then every 6 months and at the end of treatment).

    • Complete response (CR): complete resolution of all measurable or palpable PN for ≥ 28days and no appearance of new lesions.
    • Partial response (PR): A ≥ 20% reduction in the sum of the volume of all index PN lesions for ≥ 28days.
    • Stable disease (SD): A < 20% increase and < 20% decrease in the sum of the volume of all index PN lesions for ≥ 28days.
  • Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04 [ Time Frame: From the time ICF was signed until 28 days after End of Treatment (up to a maximum of 25 mon

    Original Primary Outcome: time to disease progression (TTP) based on change in volumetric MRI measurements in children and adults [ Time Frame: Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days) ]

    Current Secondary Outcome:

    Original Secondary Outcome:

    • objective radiographic responses based on volumetric MRI measurements in children and adults with NF1 and inoperable PN [ Time Frame: Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days) ]
    • feasibility and toxicity of chronic RAD001 administration in this patient population as assessed by the NCI Common Toxicity Criteria, version 4.0 [ Time Frame: From the time ICF was signed until 28 days after End of Treatment (up to a maximum of 25 months) ]
    • evaluate the clinical effect of RAD001 on clinical response by quality of life questionnaire including reduction in pain, or improvement in function or performance scale [ Time Frame: Screening, Day 1, every 3 courses, End of Study ]
    • evaluate the effect of RAD001 on skin lesions as assessed by Digital Photographs [ Time Frame: Screening, after course #3, #6, #12, #18, #24, End of Treatment ]


    Information By: Novartis

    Dates:
    Date Received: May 27, 2011
    Date Started: April 2012
    Date Completion:
    Last Updated: May 10, 2016
    Last Verified: May 2016