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

Phase 2

Terminated

Conditions: Plexiform Neurofibroma Associated With Neurofibromatosis Type 1

Interventions: Drug: Everolimus (RAD001)

Registration Number: NCT01365468

Lead Sponsor: Novartis Pharmaceuticals

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 Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Clinically definite diagnosis of NF1 according to the NIH consensus conference criteria.
Patients must have PN that have the potential to cause significant morbidity, such as lesions that could compromise the airway or the great vessels, lesions that could cause nerve compression, lesions that could result in major deformity or significant cosmetic problems
Measurable disease: patient must have at least one measurable PN amenable to volumetric MRI analysis.

Exclusion Criteria

Chronic treatment with systemic steroids or another immunosuppressive agent.
Evidence of an active optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiation therapy.
Clinical evidence of significantly impaired lung function
Pregnancy or breast feeding.
Prior therapy with mTOR inhibitors (e.g.sirolimus, temsirolimus, everolimus).
No contraindications for MRI assessments

Other protocol-defined inclusion/exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Everolimus (RAD001)	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.

Primary Outcome Measures

Name	Time	Method
Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only)	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)	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	From the time ICF was signed until 28 days after End of Treatment (up to a maximum of 25 months)	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.