This is a 36 month, multi-center, single arm, open label clinical study design. During the
treatment period (month 0-18), the safety and efficacy of 0. 1% tazarotene cream will be
compared with that of the untreated months 18-36. Daily application of the study medication
for 18 months will be for the treatment and prevention of basal cell carcinomas. Evaluations
of the face and target lesion will be done at the study centers at 3 month intervals from
months 0-36. Removal of BCCs will be done by Primary Skin Care Physicians (PSCPs) or at
study centers.
Inclusion Criteria:
The following are requirements for entry into the study:
4. 2.1 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.
4. 2.2 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 Minor criteria
1. More than 2 BCCs or one under the age of 20 years 1. Macrocephaly determined after
adjustment for height
2. Odontogenic keratocysts of the jaw proven by histology 2. Congenital malformations:
cleft lip or palate, frontal bossing, “coarse face”, moderate or severe hypertelorism
3. Three or more palmar and/or plantar pits 3. Skeletal abnormalities: Sprengel
deformity, marked pectus deformity, or marked syndactyly of the digits
4. Bilamellar calcification of the falx cerebri (if less than 20 years
old) 4. Radiological abnormalities: bridging of the sella turcica, vertebral
anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies,
modeling defects of the hands and feet, or flame shaped lucencies of the hands or
feet
5. Fused, bifid, or markedly splayed ribs. 5. Ovarian fibroma
6. First degree relative with basal cell nevus syndrome (BCNS) 6. Medulloblastoma
7. PTCH1 gene mutation in normal tissue*
*modification of criteria outlined by Kimonis et al, Am J Med Genetics 69: 299-308,
1997
4. 2.3 The subject is from 18-75 years of age, inclusive.
4. 2.4 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.
4. 2.5 The subject must sign and date all informed consent statements.
4. 2.6 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. For example, topical preparations
containing corticosteroids (other than
1% hydrocortisone applied no more than 6 times per month) or vitamin A derivatives
are not allowed. Moisturizers and emollients are allowable. Subjects will be
encouraged to use sunscreen (SPF 15) at least once daily on all exposed skin sites.
4. 2.7 The subject is willing to contact the study center after each PSCP visit to
inform the center re the occurrence of the visit and re any treatment of skin tumors.
4. 2.8 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.
Exclusion Criteria:
4. 3.1 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 1% hydrocortisone on no more than 36 days
during the six months prior to study entry), (ii) retinoids (e. g., etretinate,
isotretinoin, tazarotene, tretinoin, adapalene) systemically or topically to the chest
or back during the six months prior to study entry (except for subjects concurrently
enrolled in Trial 1- Chemoprevention Trial); (iii) alpha-hydroxy acids (e. g., glycolic
acid, lactic acid) (iv) 5-fluorouracil or imiquimod (except as treatment to discrete
BCCs) systemically or topically to the chest or back during the six months prior to
study entry. (v) any systemic investigational medication or any topical
investigational medication to the chest or back within 30 days prior to randomization
or is scheduled to receive a systemic investigational medication or a topical
investigational medication, other than tazarotene, to the chest or back during the
course of the study. (vi) treatment with systemic chemotherapy within one year prior
to starting study medication.
4. 3.2 The subject has a history of hypersensitivity to any of the ingredients in the
study medication formulations.
4. 3.3 The subject is unable to return for follow-up tests.
4. 3.4 The subject has uncontrolled systemic disease, including known HIV positive
patients.
4. 3.5 The subject has a history of other skin conditions or significant illness that
would interfere with evaluation of the study medication.
4. 3.6 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.
4. 3.7 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.
