Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01412892
• Date of registration: 08/08/2011
• Prospective Registration: No
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas NFitor
• Scientific title: A Single Arm, Multicenter Phase II a Trial of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas That Cannot be Removed by Surgery
• Date of first enrolment: April 2011
• Target sample size: 30
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01412892
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Pierre Wolkenstein, MD, PhD
• Affiliation: Assistance Publique - Hôpitaux de Paris

Key inclusion & exclusion criteria

Inclusion Criteria:

- Clinical diagnosis of NF1, according to NIH criteria, with internal plexiform
neurofibroma (PN) and at least 1 of criteria for NF1:

6 or more café-au-lait spots Freckling in the axilla or groin Optic glioma 2 or more
Lisch nodules Distinctive bony lesion

1-degree relative with NF1

- At least 1 inoperable PN(s) that has/have the potential to cause significant
morbidity: Paravertebral lesions that could compromise the spinal cord Head and neck
lesions that could compromise the airway or great vessels Brachial or lumbar plexus
lesions that could cause nerve compression and loss of function Lesions that could
result in major deformity (e.g., orbital lesions) or significant cosmetic problems
Lesions of the extremity that cause limb hypertrophy or loss of function Painful
lesions

- Complete resection of a PN with acceptable morbidity is not feasible OR patient
refuses surgery OR the number of PNs leads to not feasible surgery according to the
steering committee's site

- Measurable PN amenable to volumetric MRI analysis using fusion of images

- Measurable lesion (at least 3 cm in one dimension)

- Karnofsky >70%

- 18= Age =60

- absolute neutrophil count (ANC) =1.5x109/L, Platelets =100x109/L, Hb >9g/dL

- bilirubin: =1.5xULN, ALT and AST =2.5xULN unless evident Gilbert disease (amendment
n°2). For patients with known liver metastases: AST and ALT = 5xULN

- Creatinine = 1.5xULN

- Life expectancy = 2 years

- Cholesterol =300 mg/dL or =7.75 mmol/L and triglycerides = 2.5x ULN

- Women of childbearing potential must have had a negative serum pregnancy test within
7 days and a negative urine pregnancy test within 72 hours prior to the
administration of RAD001 start and must use an effective birth control method.

- Men should use condoms and their partner(s) use an effective birth control method

- A written informed consent obtained

Exclusion Criteria:

Patients who/with:

- have previously received mTOR inhibitors

- a known hypersensitivity to RAD001 or other rapamycin or to its excipients

- receiving chronic systemic treatment with corticosteroids or another
immunosuppressive agent. (Dose equivalent to 10 mg/day of methylprednisone), topical
steroids or organotherapy for bilateral adrenalectomy are acceptable

- a known history of HIV seropositivity

- acute viral hepatitis

- autoimmune hepatitis

- with an active, bleeding diathesis. Patients may use coumadin or heparin preparations

- have any severe and/or uncontrolled medical conditions or other conditions that could
affect their participation

- have a history of another primary malignancy =3 years, with the exception of
non-melanoma skin cancer and carcinoma in situ of the uterine cervix

- Female patients who are pregnant or breast feeding, or adults of reproductive
potential who are not using effective birth control methods. If barrier
contraceptives are being used, these must be continued throughout the trial by both
sexes. Oral contraceptives are not acceptable alone

- a contraindication to MRI

- are using other investigational agents or who had received investigational drugs = 4
weeks prior to study treatment start

- unwilling or unable to comply with the protocol

- not affiliated to health system



Age minimum: 18 Years
Age maximum: 60 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Neurofibromatosis Type 1

Plexiform Neurofibroma

Neurofibromatoses

Intervention(s)

Drug: RAD001: Everolimus

Primary Outcome(s)

Radiographic response assessed by MRI analysis [Time Frame: after 1 year of treatment]

Secondary Outcome(s)

performance of physical examinations [Time Frame: At 2 years]

Radiographic response assessed by MRI analysis [Time Frame: At 2 years]

laboratory evaluations [Time Frame: At 2 years]

adverse events [Time Frame: At 2 years]

measurement of vital signs [Time Frame: At 2 years]

all concomitant medications and therapies [Time Frame: At 2 years]

Deficiency [Time Frame: At 2 years]

Pain [Time Frame: At 2 years]

Overall survival [Time Frame: At 2 years]

Quality of life [Time Frame: At 2 years]

Secondary ID(s)

2010-023137-34

P090502

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Novartis