Efficacy and Safety of RAD001 in Treating Plexiform Neurofibromas (PN) Associated With Neurofibromatosis (NF1)
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 :
determine whether RAD001, administrated orally daily on a continuous dosing schedule might:
- Increases time to disease progression (TTP) based on volumetric MRI measurements in children and adults with NF1 in inoperable documented progressive PN (stratum 1).
- 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
- 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.
Plexiform Neurofibroma Associated With Neurofibromatosis Type 1
Drug: Everolimus (RAD001)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of RAD001 in the Treatment of Patients With Plexiform Neurofibromas (PN) Associated With Neurofibromatosis Type 1 (NF1)|
- 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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: Yes ]
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 months) ] [ Designated as safety issue: Yes ]Adverse events were assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0. If CTCAE grading does not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to grades 1 - 4 respectively, were used. CTCAE grade 5 (death) was not used in this study.
- Number of Patients With Clinical Response [ Time Frame: Screening, Day 1, after course #3, #6, #12, #18, #24, End of Treatment (1 course = 28 days) ] [ Designated as safety issue: Yes ]Clinical response is defined as improvement of function, performance status, or decrease in PN related pain persisting for at least 28 days on treatment.
- Physician's Global Assessment of Clinical Condition (PGA) of Skin Lesions [ Time Frame: Screening, after course #3, #6, #12, #18, #24, End of Treatment (1 course = 28 days) ] [ Designated as safety issue: No ]The Physician‟s Global Assessment of Clinical Condition (PGA) is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the patient‟s skin disease as compared to baseline. Responses must be confirmed by at least two assessments separated in time by at least 4 weeks. The grading ranges from 0 to 6; 0 is Completely clear where as 6 is for worse condition. A complete clinical response (CCR) requires a grading of 0 indicating the absence of disease (histological confirmation is not required). Grades 1, 2, and 3 constitute partial response, indicating improvement of at least 50 percent, but less than 100 percent improvement.
|Study Start Date:||April 2012|
|Study Completion Date:||April 2015|
|Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Experimental: Everolimus (RAD001)
enrolled patients received everolimus (RAD001) in an open label manner. Recommended starting dose of everolimus depend on body surface area, starting from 2.5 mg once daily to 7.5 mg once daily.
Drug: Everolimus (RAD001)
oral daily dosing of tablet starting with 2.5 mg
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01365468
|Novartis Investigative Site|
|Tel-Aviv, Israel, 6423906|
|Novartis Investigative Site|
|Tel-Hashomer, Israel, 52621|
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|