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

Primary Purpose

Plexiform Neurofibroma Associated With Neurofibromatosis Type 1

Status

Terminated

Phase

Phase 2

Locations

Israel

Study Type

Interventional

Intervention

Everolimus (RAD001)

About this trial

This is an interventional treatment trial for Plexiform Neurofibroma Associated With Neurofibromatosis Type 1 focused on measuring RAD001,, Everolimus,, Plexiform Neurofibroma,, Neurofibromatosis Type 1

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Everolimus (RAD001)

Arm Description

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.

Outcomes

Primary Outcome Measures

Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only)

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)

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

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01365468

First Posted

May 27, 2011

Last Updated

May 10, 2016

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01365468

Brief Title

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

2. Study Status

Record Verification Date

May 2016

Overall Recruitment Status

Terminated

Why Stopped

Poor patients' accrual

Study Start Date

April 2012 (undefined)

Primary Completion Date

April 2015 (Actual)

Study Completion Date

April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

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 : 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Plexiform Neurofibroma Associated With Neurofibromatosis Type 1

Keywords

RAD001,, Everolimus,, Plexiform Neurofibroma,, Neurofibromatosis Type 1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Everolimus (RAD001)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Everolimus (RAD001)

Intervention Description

oral daily dosing of tablet starting with 2.5 mg

Primary Outcome Measure Information:

Title

Time to Disease Progression (TTP) Based on Change in Volumetric MRI Measurements in Children and Adults (In Stratum I Only)

Description

Time Frame

Screening, after course #6, #12, #18, #24, End of Treatment(1 course=28days)

Title

Number of Patients With Objective Radiographic Responses Based on Volumetric MRI Measurements (In Stratum 2 Only)

Description

Time Frame

Screening, after course #6, then every 6 months and end of treatment(1 course=28days)

Title

Number of Patients With Adverse Events Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) V.04

Description

Time Frame

From the time ICF was signed until 28 days after End of Treatment (up to a maximum of 25 months)

Other Pre-specified Outcome Measures:

Title

Number of Patients With Clinical Response

Description

Clinical response is defined as improvement of function, performance status, or decrease in PN related pain persisting for at least 28 days on treatment.

Time Frame

Screening, Day 1, after course #3, #6, #12, #18, #24, End of Treatment (1 course = 28 days)

Title

Physician's Global Assessment of Clinical Condition (PGA) of Skin Lesions

Description

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.

Time Frame

Screening, after course #3, #6, #12, #18, #24, End of Treatment (1 course = 28 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Tel-Aviv

ZIP/Postal Code

6423906

Country

Israel

Facility Name

Novartis Investigative Site

City

Tel-Hashomer

ZIP/Postal Code

52621

Country

Israel

12. IPD Sharing Statement

Learn more about this trial

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

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