Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T

Qualifying subjects will have a diagnosis of Neurofibromatosis 1 and have disfiguring
cutaneous lesions that can be measured by photography. The subjects will have photographs of
the target lesions,biopsies of the lesions,and safety blood laboratory tests at 3 time
points (baseline, 3 months and 6 months which is end of treatment). Everolimus will be taken
orally for 6 months. Subjects will visit the clinic monthly for an exam and adverse event
evaluation. Laboratory testing will be done at these visits if determined necessary by the
PI.

Inclusion Criteria:

1. Patient is at least 18 years of age at the time of enrollment

2. Informed consent

3. Compliance with trial requirements (photography, lab draws, medication schedules, and
study visits)

4. Diagnosis of NF 1 and has cutaneous neurofibromas that are located in in a region
amenable to photography

5. Females of child bearing potential must not be pregnant as confirmed by a negative
pregnancy test (blood beta-hCG level) prior to study enrollment and must agree to use
appropriate contraceptive methods for the duration of the trial

6. Patient must have adequate liver function as shown by, total bilirubin ALT and AST
8. Patient must have adequate renal function, serum creatinine must have adequate lipid profile, fasting serum cholesterol mmol/L, fasting triglycerides
Exclusion Criteria:

1. Patients currently receiving anticancer therapies or who have received anticancer
therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation
therapy, antibody based therapy, etc.) 2. Known intolerance or hypersensitivity to
Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) 3. Known impairment
of gastrointestinal (GI) function or GI disease that may significantly alter the
absorption of oral Everolimus 4. Uncontrolled diabetes mellitus despite adequate therapy
5. Patients who have any severe and /or uncontrolled medical conditions such as: unstable
angina pectoris, symptomatic congestive heart failure, myocardial infarction start of Everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically
significant cardiac disease, symptomatic congestive heart failure of New York Hear
Association Class III or IV, known active (acute or chronic) or uncontrolled severe
infection, liver disease such as cirrhosis, decompensated liver disease, or chronic
hepatitis, known severely impaired lung function (spirometry and DLCO 50% or less of
normal and O2 saturation 88% or less at rest on room air), active, bleeding diathesis,
chronic treatment with corticosteroids, or other immunosuppressive agents, topical or
inhaled corticosteroids are allowed, know history of HIV seropositivity, patients who have
received live attenuated vaccines within 1 week of start of Everolimus. Patient whould
avoid close contact with others who have received live attenuated vaccines during the
study, patients who have a history of primary malignancy, with the exceptions of
mon-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which
the patient has been disease free for >/- 3 years, patients with a history of non
compliance to medical regimens or who are considered potentially unreliable or will not be
able to complete the entire study, patients who are currently part of or have participated
in any clinical investigation with an investigational drug within 1 month prior to dosing,
pregnant or nursing (lactating) women, women of child-bearing potential (WOCBP), defined
as all women physiologically capable of becoming pregnant, unless they are using highly
effective methods of contraception during dosing of study treatment. highly effective
contraception methods,male patients whose sexual partner(s) are WOCBP who are not willing
to use adequate contraception, during the study and for 8 weeks after the end of
treatment.