Clinical trial NCT01365468: Efficacy and Safety of RAD001 in Treating Plexiform Neurofibromas (PN) Associated With Neurofibromatosis (NF1)
Official title: A Phase II Study of RAD001 in the Treatment of Patients With Plexiform Neurofibromas (PN) Associated With Neurofibromatosis Type 1 (NF1)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Plexiform Neurofibroma Associated With Neurofibromatosis Type 1
Keywords: RAD001,
Everolimus,
Plexiform Neurofibroma,
Neurofibromatosis Type 1
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-06-03
Enrollment: 9
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Clinically definite diagnosis of NF1 according to the NIH consensus conference criteria.
2. 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
3. Measurable disease: patient must have at least one measurable PN amenable to volumetric MRI analysis.

Exclusion Criteria:

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

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only)
timeFrame: Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days)
measure: Number of Patients With Objective Radiographic Responses Based on Volumetric MRI Measurements (In Stratum 2 Only)
timeFrame: Screening, after course #6, then every 6 months and end of treatment(1 course=28days)
measure: Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04
timeFrame: From the time ICF was signed until 28 days after End of Treatment (up to a maximum of 25 months)
Secondary outcomes:
Other outcomes:
measure: Number of Patients With Clinical Response
timeFrame: Screening, Day 1, after course #3, #6, #12, #18, #24, End of Treatment (1 course = 28 days)
measure: Physician's Global Assessment of Clinical Condition (PGA) of Skin Lesions
timeFrame: Screening, after course #3, #6, #12, #18, #24, End of Treatment (1 course = 28 days)
Locations:
city: Tel-Aviv
country: Israel
facility: Novartis Investigative Site
city: Tel-Hashomer
country: Israel
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: