Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T
Condition: Neurofibromatosis 1
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
Intervention: Everolimus
Intervention description: Everyone in the study will receive Everolimus at a starting dose of 10 mg daily and will be adjusted up or down by 2.5 mg at 2 week intervals to attain a trough concentration of 5-15 ng/ml
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neurofibroma; NF-1; Everolimus; mTOR inhibitor

Summary:

      This trial is evaluating the use of oral Everolimus to determine if there is a reduction in
      the size of the disfiguring cutaneous lesions in patients with Neurofibromatosis 1 over a 6
      month period. The evaluation will be done by 3D photography measuring volume with the LIFEVIZ
      Micro system.
    

Eligibility criteria:

        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 </= 2.0 mg/dL,
             ALT and AST </= 2.5 X ULN, INR </= 2

        8. Patient must have adequate renal function, serum creatinine </= 1.5 X ULN 9. Patient
        must have adequate lipid profile, fasting serum cholesterol </= 300 mg/dL OR </= 7.75
        mmol/L, fasting triglycerides </= X ULN

        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 </= prior to 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 would 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.

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