Topical Sirolimus in Patients With Basal Cell Nevus Syndrome and in Healthy Participants

DISEASE CHARACTERISTICS:

* Patient

  * Confirmed diagnosis of basal cell nevus syndrome (BCNS)
  * Known patched (PTCH) gene mutation

    * Must have full sequence of coding exons with intron/exon junctions in the PTCH gene OR prior genetic testing confirming PTCH mutation by the Yale University DNA Diagnostics Laboratory
* Age- and sex-matched healthy participant (control)

  * Unaffected relative of patient OR normal healthy volunteer with no family history of BCNS or features of BCNS

    * No unrelated healthy participant meeting any of the following clinical criteria for BCNS:

      * Lamellar calcification of the falx cerebri
      * Prior odontogenic keratocyst or any jaw cyst for which a histopathologic diagnosis cannot be ascertained
      * Palmar or plantar pits typical of BCNS
      * More than 3 basal cell carcinomas (BCC) in a lifetime or 1 BCC under the age of 30
      * History of medulloblastoma
    * No unrelated healthy participant with 2 or more of the following features:

      * History of ovarian or cardiac fibroma
      * Mesenteric or pleural cysts
      * Polydactyly
      * Macrocephaly determined after adjustment for height
      * Craniofacial features of BCNS, including cleft palate, frontal bossing, hypertelorism, iris coloboma or other developmental defects of the eye, or coarse facies
      * Vertebral anomalies, including spina bifida occulta outside the lumbar region
      * Bifid or splayed ribs
      * Other radiographic findings, including bridging of the sella turcica, nonlamellar calcification of the falx cerebri, or flame-shaped lucencies in the phalanges = 1-3 BCCs over the age of 30

PATIENT CHARACTERISTICS:

* WBC ≥ 4,000/mm³
* Neutrophil count ≥ 2,000/mm³
* Platelet count ≥ 150,000/mm³
* Hemoglobin ≥ 11.5 g/dL
* Bilirubin 0.3-1.0 mg/dL
* AST 17-59 U/L
* PTT 10-13 seconds OR INR 1.0-1.4
* Creatinine clearance \> 50 mL/min
* Cholesterol \< 350 mg/dL
* Triglycerides \< 400 mg/dL
* Not pregnant or nursing
* Negative pregnancy test
* Fertile participants must use effective contraception for ≥ 1 month before, during, and for ≥ 12 weeks after study treatment
* No active infection
* No alcohol or drug abuse
* No psychiatric disorder or mental deficiency that would preclude study compliance
* No uncontrolled hypertension (i.e., blood pressure \> 140/90 mm Hg on \> 2 measurements)
* No chronic active infection requiring treatment
* No untreated reactive purified protein derivative of tuberculin (PPD)
* No HIV-1 infection
* No infection requiring antibiotics within the past 30 days
* No other skin disease affecting broad areas of the body, including the region to be treated and biopsied
* No known hepatitis B or C infection (detectable RNA off antiviral therapy)
* No immune deficiency disorder
* No known hypersensitivity to sirolimus or macrolide antibiotics (e.g., erythromycin, azithromycin, or clarithromycin)
* No cancer within the past 5 years except basal cell skin cancer

PRIOR CONCURRENT THERAPY:

* At least 1 month since prior investigational drugs
* No concurrent dietary supplements, including Hypericum perforatum (St. John's wort) or megadose vitamins
* No other concurrent immunosuppressive medications, including corticosteroids
* No concurrent medications known to interfere with sirolimus metabolism
* No concurrent anticoagulants
* No concurrent acetylsalicyclic acid or other drugs affecting platelet function or number
* No routine (i.e., \> 2 doses/week) use of nonsteroidal anti-inflammatory drugs
* No drugs or substances that would effect sirolimus blood concentrations, including any of the following:

  * Nicardipine
  * Verapamil
  * Clotrimazole
  * Fluconazole
  * Itraconazole
  * Troleandomycin
  * Cisapride
  * Metoclopramide
  * Clarithromycin
  * Erythromycin
  * Bromocriptine
  * Cimetidine
  * Danazol
  * HIV-protease inhibitors (e.g., ritonavir or indinavir)
  * Phenobarbital
  * Carbamazepine
  * Phenytoin
  * Rifabutin
  * Rifapentine
  * Grapefruit juice
  * Vaccinations (especially live vaccines)