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

NCT01365468 | Terminated Phase 2 Results

• 1 other identifier: CRAD001MIL04T
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

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. 1.determine whether RAD001, administrated orally daily on a continuous dosing schedule might:
2. 2.Increases time to disease progression (TTP) based on volumetric MRI measurements in children and adults with NF1 in inoperable documented progressive PN (stratum 1).
3. 3.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
4. 4.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.

Conditions

Plexiform Neurofibroma Associated With Neurofibromatosis Type 1

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

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

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

Other Outcomes (2)

• Number of Patients With Clinical Response

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

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

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

Study Arms (1)

Everolimus (RAD001)

EXPERIMENTAL

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)

Interventions

Everolimus (RAD001) DRUG

oral daily dosing of tablet starting with 2.5 mg

Everolimus (RAD001)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Tel Litwinsky, 52621, Israel

Location

MeSH Terms

Conditions

Neurofibroma, Plexiform; Neurofibromatosis 1

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Neurofibromatoses; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Study got terminated because of poor patient's accrual.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2011
• First Posted: June 3, 2011
• Study Start: April 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 12, 2016
• Results First Posted: May 12, 2016

Record last verified: 2016-05

Locations

IL (2)