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Trial record 17 of 32 for:    "Nevoid basal cell carcinoma syndrome"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00433485
Recruitment Status : Completed
First Posted : February 12, 2007
Last Update Posted : September 23, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE February 8, 2007
First Posted Date  ICMJE February 12, 2007
Last Update Posted Date September 23, 2016
Study Start Date  ICMJE Not Provided
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2007)
  • Alterations in RNA as measured by microarray analysis
  • Alterations in protein expression as measured by 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectroscopy
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00433485 on Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Topical Sirolimus in Patients With Basal Cell Nevus Syndrome and in Healthy Participants
Official Title  ICMJE In Vivo and In Vitro Pharmacology of Sirolimus in Subjects With Basal Cell Nevus Syndrome
Brief Summary

RATIONALE: Studying samples of blood and tissue from patients with basal cell nevus syndrome and from healthy participants in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to basal cell nevus syndrome. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of sirolimus may keep basal cell skin cancer from forming in patients with basal cell nevus syndrome.

PURPOSE: This phase I trial is studying topical sirolimus in patients with basal cell nevus syndrome and in healthy participants.

Detailed Description



  • Compare messenger RNA and protein expression patterns in patients with basal cell nevus syndrome (BCNS) vs in cultured cells of healthy participants (control) before treatment to identify a set of genes that are differentially expressed in BCNS.
  • Assess the effects of topical sirolimus on gene expression (genes identified in the primary objective) in vivo using keratinocytes, fibroblasts, and lymphocytes from patients with BCNS and from healthy participants (controls) by targeted expression methods.

OUTLINE: Patients and healthy participants receive topical sirolimus ointment twice daily for 12 weeks.

Blood and skin biopsies are obtained at baseline and at week 12 for gene and protein expression studies. Alterations in RNA are measured by microarray analysis. Alterations in protein expression are measured by 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

After completion of study therapy, patients and healthy participants are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 16 patients and healthy participants will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Neoplastic Syndrome
  • Non-melanomatous Skin Cancer
Intervention  ICMJE
  • Drug: sirolimus
  • Genetic: comparative genomic hybridization
  • Genetic: gene expression analysis
  • Genetic: microarray analysis
  • Genetic: protein expression analysis
  • Genetic: proteomic profiling
  • Other: laboratory biomarker analysis
  • Other: mass spectrometry
  • Procedure: biopsy
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: February 8, 2007)
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2008
Actual Primary Completion Date March 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • 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


  • 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


  • 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00433485
Other Study ID Numbers  ICMJE CDR0000522464
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Allen E. Bale, MD Yale University
PRS Account Yale University
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP