Topical Tazarotene in Treating Patients With Basal Cell Skin Cancer and Basal Cell Nevus Syndrome on the Chest and Back

OBJECTIVES:

Primary

- To expand and refine chemopreventive strategies in individuals with basal cell nevus
syndrome (BCNS) on the chest and back, who are at high risk for the development of
basal cell carcinomas (BCCs).

- To determine whether tazarotene 0.1% cream applied to the chest for two years will
reduce the numbers of basal cell carcinomas (BCCs) observed, as compared to the number
expected, based on changes in BCC numbers observed during months 0-12.

Secondary

- To compare the difference in total BCC burden (measured as the total lesion surface
area) between chest and back over various time points and aggregated intervals of
interest.

- To determine whether there are any detectable wash-in or wash-out periods for the
tazarotene effects.

- Explore the use of a random effects model for longitudinal analysis of total lesions
over time.

OUTLINE: This is a multicenter study. Patients are randomized into 1 of 2 arms.

- Arm I: Patients apply 0.1% tazarotene cream on months 0-12 and vehicle (placebo) on
months 13-36 once daily to the chest in the absence of disease progression or
unacceptable toxicity.

- Arm II: Patients apply vehicle (placebo) on months 0-12 and 0.1% tazarotene cream on
months 13-36 once daily to the chest in the absence of disease progression or
unacceptable toxicity.

Treated chest and untreated back is evaluated at 3 month intervals for 36 months.

List of Inclusion Criteria:

1. Study subjects must have at least one basal cell carcinoma ≥ 3mm in diameter (target
lesion) on any area of the skin except the face, chest, and back (and not impinging
on vital sites) diagnosed clinically by a Study Investigator at the baseline visit.

2. Study subjects must meet diagnostic criteria for basal cell nevus syndrome including
major criterion #1 plus one additional major criterion or two of the minor criteria
outlined in Table I. A first degree relative would satisfy BCNS diagnostic criteria
with any two major criteria or any single major plus two minor criteria.

Table I. BCNS Diagnostic Criteria

Major criteria

1. More than 2 BCCs or one under the age of 20 years

2. Odontogenic keratocysts of the jaw proven by histology

3. Three or more palmar and/or plantar pits

4. Bilamellar calcification of the falx cerebri (if less than 20 years old)

5. Fused, bifid, or markedly splayed ribs.

6. First degree relative with basal cell nevus syndrome (BCNS)

7. PTCH1 gene mutation in normal tissue*

Minor criteria

1. Macrocephaly determined after adjustment for height

2. Congenital malformations: cleft lip or palate, frontal bossing, "coarse face."

3. Skeletal abnormalities: Sprengel deformity, marked pectus deformity

4. Radiological abnormalities: bridging of the sella turcica, vertebral anomalies such
as hemivertebrae, fusion or elongation of the vertebral bodies.

5. Ovarian fibroma

6. Medulloblastoma

3.The subject is from 18-75 years of age, inclusive.

4. If the subject is female and of child-bearing potential (women are considered not of
childbearing potential if they are at least 2 years post-menopausal and/or surgically
sterile), she:

i. has been using adequate contraception (abstinence, IUD, birth control pills, or
spermicidal gel with diaphragm or condom) since her last menses and will use adequate
contraception during the study, and ii. is not lactating, and iii. has documented one
negative serum pregnancy test within 14 days prior to study entry.

5. The subject is willing to abstain from application of non-study topical medications to
the skin of the face for the duration of the study, including prescription and over the
counter preparations.

6. The subject is willing not to have targeted BCCs treated by their PSCP 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.

List of Exclusion Criteria:

1. The subject has used topical or systemic therapies that might interfere with the
evaluation of the study medication during the study.

2. The subject has a history of hypersensitivity to any of the ingredients in the study
medication formulations.

3. The subject is unable to return for follow-up tests.

4. The subject has uncontrolled systemic disease, including known HIV positive patients.

5. The subject has a history of other skin conditions or significant illness that would
interfere with evaluation of the study medication.

6. 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.

7. The subject has a history of invasive cancer within the past five years excluding
non-melanoma skin cancer, Stage I cervical cancer, or CLL Stage 0.