Green Tea Extract in Treating Patients With Actinic Keratosis

OBJECTIVES: I. Determine the efficacy of the green tea extract epigallocatechin gallate
(Polyphenon E topical ointment) in causing complete clinical and histopathologic regression
in patients with actinic keratoses. II. Determine duration of treatment with Polyphenon E
necessary to cause regression in these patients. III. Describe pathophysiologic and molecular
alterations in actinic keratoses and sun damaged skin that are not present in skin that is
not sun damaged in these patients. IV. Determine the effects of this treatment on biomarkers
for skin cancer in these patients.

OUTLINE: This is a randomized, double blind, placebo controlled study. One of the patient's
arms is randomized to receive topical epigallocatechin gallate (Polyphenon E), the other arm
to receive a placebo. Patients receive topical applications daily for 12 weeks, or until
resolution of all actinic keratoses within the treatment field.

PROJECTED ACCRUAL: A minimum of 60 patients will be accrued for this study over 10 months.

Inclusion Criteria:

1. participants multiple sites of actinic keratosis identified by clinical examination
and the histologic confirmation of one lesion (Grade 1-3 as defined previously in
"Clinical Grading") are eligible.

2. No history of invasive cancer within 5 years (though non-melanoma skin cancer, stage I
cervical cancer, or chronic lymphocytic leukemia (CLL) stage 0 will not be reason to
exclude a patient); no severe metabolic disorders or other life-threatening acute or
chronic disease; no additional x-ray or chemotherapy anticipated.

3. Not requiring use of topical medications in areas being studied.

4. Subjects must meet the Southwest Oncology Group performance status criteria of 0 - 1
(0= fully active, able to carry on all pre-disease activities without restriction
[Karnofsky scale 90 - 100]; 1 = restricted in physically strenuous activity, but
ambulatory and able to carry out work of a light or sedentary nature, i.e. light
housework or office work [Karnofsky scale 70 - 80]).

5. Signed informed consent approved by the local Human Subjects Committee (Institutional
Review Board).

Exclusion Criteria:

1. Use of the following systemic or local therapies for the periods specified, prior to
entry into the study:

Within 2 weeks: topical medications, e.g. corticosteroids, alpha-hydroxyacids
(glycolic acid, lactic acid) or retinoids (Retin-A) to the target lesions Within 4
weeks: systemic steroid therapy. Within 2 months: cryotherapy to the target lesions,
laser resurfacing, chemical peels, topical application of 5-fluorouracil (5-FU) or
masoprocol (Actinex) for treatment of actinic keratoses. Systemic treatment with
chemotherapeutic agents, psoralens, immunotherapy, retinoids (Tegison, Accutane).

2. Any medical condition which , in the opinion of the investigator, could preclude study
participation

3. Active infectious diseases such as tuberculosis (TB) or HIV that may affect the
patient systemically and may also affect the immune system. Localized, minor
infections such as sinusitis, uncomplicated urinary tract infection, otitis media,
etc. will not be criteria for exclusion from the study.

4. Use of any investigational drug in the previous 30 days.

5. Any history of keloid formation.

6. Pregnant or nursing patients.

7. Participants who may be unreliable for the study, including those engaging in
excessive alcohol intake or drug abuse, or participants who are unable to return for
scheduled follow-up visits