To Determine The Efficacy and Safety of GDC-0449 in Patients With Basal Cell Nevus Syndrome (BCNS)
Condition: Basal Cell Nevus Syndrome; Gorlin Syndrome
MeSH terms: Nevus; Basal Cell Nevus Syndrome; Nevus, Pigmented; Syndrome
Intervention: GDC-0449
Intervention description: capsule, 150 mg, one pill daily, 18 months
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 41.0
Sex: All
Minimum age: 35 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to reduce the number of new surgically eligible BCCs by 50%
      appearing during month 3-18 of medication ingestion.
    

Eligibility criteria:

        Inclusion Criteria:

        The subject:

          -  has had diagnosed at least 10 SEB (of diameter 3 mm diameter or greater on the nose or
             periorbital skin, 5 mm or greater elsewhere on the face, or 9 mm or greater on
             non-facial areas excluding the skin below the knees) during the two years before study
             entry, as documented histologically in physicians' records and/or diagnosed clinically
             by a Study Investigator at baseline.

          -  meet diagnostic criteria for basal cell nevus syndrome

          -  is willing to abstain from application of non-study topical medications to the skin
             for the duration of the study, including prescription and over the counter
             preparations. Subjects will be encouraged to use sunscreen (SPF 15) at least once
             daily on all exposed skin sites.

          -  is willing to forego treatment of BCCs unless the BCCs are documented by Study
             Investigators, preferably on two separate visits, except when the PSCP believes that
             delay in treatment potentially might compromise the health of the subject.

          -  has normal laboratory tests as defined by the following: Normal hematopoietic
             capacity, Normal hepatic function: AST and ALT greater than or equal to 2x the upper
             limit of normal (ULN) Total bilirubin within normal range 0.20 mg/dl to 1.50 mg/dl or
             within 3x ULN for patients with Gilbert's disease Normal renal function: normal serum
             creatinine or measured creatinine clearance less than 50 mL/minute. Fasting
             cholesterol greater than or equal to 220 untreated

          -  be willing to not donate blood or semen for three months following discontinuation of
             Study medications.

          -  is willing to avoid pregnancy in his partner as defined by the following: Male subject
             is willing to use a latex condom during the study and for 3 months after the last dose
             during sexual contact with a female of childbearing potential, even if he has had a
             successful vasectomy. His partner must also use a form of birth control

        Exclusion Criteria:

        The subject:

          -  has used topical or systemic therapies that might interfere with the evaluation of the
             study medication during the study. Specifically these include the use of: (i)
             glucocorticoids to more than 5% of the skin (ii) retinoids systemically or topically
             to more than 5% of the skin during the six months prior to study entry; (iii)
             alpha-hydroxy acids to more than 5% of the skin during the six months prior to study
             entry (iv) 5-fluorouracil or imiquimod systemically or topically to the skin above the
             knees during the six months prior to study entry. (v) treatment with systemic
             chemotherapy within one year prior to starting study medication.

          -  has a history of hypersensitivity to any of the ingredients in the study medication
             formulations.

          -  is unable to return for follow-up visits and tests.

          -  has uncontrolled systemic disease, including known HIV positive patients.

          -  has history of congestive heart failure.

          -  has uncontrolled hypocalcemia, hypomagnesemia, or hypokalemia

          -  has clinically important history of liver disease, including viral or hepatitis,
             current alcohol abuse, or cirrhosis.

          -  has any condition or situation which in the Investigator's opinion may put the subject
             at significant risk, could confound the study results, or could interfere
             significantly with the subject's participation in the study.

          -  has a history of invasive cancer within the past five years excluding non-melanoma
             skin cancer, Stage I cervical cancer, ductal carcinoma in situ of the breast, or CLL
             Stage 0.

          -  has current, recent (within 4 weeks of Day 1), or planned participation in an
             experimental drug study while enrolled in this study.

          -  is a female who is pregnant, plans to ever to become pregnant, capable of becoming
             pregnant or is breast feeding.

          -  is a male who is unwilling or unable to comply with pregnancy prevention measures.