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

NCT00433485 | Completed Phase 1

• 2 other identifiers: CDR0000522464YALE-HIC-26866
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Neoplastic Syndrome; Non-melanomatous Skin Cancer

Keywords

basal cell carcinoma of the skin; nevoid basal cell carcinoma syndrome

Outcome Measures

Primary Outcomes (2)

• 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

Interventions

sirolimus DRUG

comparative genomic hybridization GENETIC

gene expression analysis GENETIC

microarray analysis GENETIC

protein expression analysis GENETIC

proteomic profiling GENETIC

laboratory biomarker analysis OTHER

mass spectrometry OTHER

biopsy PROCEDURE

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Yale University: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Neoplasms; Carcinoma, Basal Cell; Basal Cell Nevus Syndrome

Interventions

Sirolimus; Comparative Genomic Hybridization; Gene Expression Profiling; Microarray Analysis; Mass Spectrometry; Biopsy

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Basal Cell; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Cytogenetic Analysis; Genetic Techniques; Investigative Techniques; Molecular Diagnostic Techniques; Nucleic Acid Hybridization; Microchip Analytical Procedures; Chemistry Techniques, Analytical; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Allen E. Bale, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: PREVENTION
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2007
• First Posted: February 12, 2007
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: September 23, 2016

Record last verified: 2016-09