Trial Comparing the Effects of Intermittent Vismodegib vs. PDT in Patients With Multiple Basal Cell Carcinomas

This is a Phase II, 28 month, randomized, two arm multicenter clinical study design. During
the initial 7 months of the study, all 24 subjects will receive vismodegib, 150mg/day. They
then will be randomized in a 1:1 ratio to receive intermittent vismodegib, 150 mg/day,
during months 10-13, 16-19, and 22-25 or to receive treatment with PDT at month 10 and at
three month intervals thereafter. The safety and efficacy of intermittent vismodegib and of
PDT will be assessed at the time of the subjects' visits to the Study Center and at the time
of telephone contacts. A Data Safety Monitoring Board (DSMB) will review results for an
interim analysis when 12 subjects have completed 28 months. The DSMB review will focus on
adverse events and efficacy results. Subjects will be monitored for the presence of
surrogate endpoint biomarkers (SEBs) at each Study visit.

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.

- 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. For example, topical preparations containing
corticosteroids (other than Triamcinolone applied no more than 6x/month).

- 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 (other than Triamcinolone on no more than 36 days during the six
months prior to study entry) 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.