Clinical trial NCT00005097: Green Tea Extract in Treating Patients With Actinic Keratosis
Official title: A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of Polyphenon E Against Various Endpoints of Actinic Keratosis Pathobiology
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-melanomatous Skin Cancer
Keywords: squamous cell carcinoma of the skin
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-02
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will have actinic keratosis on both arms and apply Polyphenon E topical ointment on one arm and placebo ointment to apply to the other arm. Subjects will serve as their own control by being unaware of which arm will have the active study drug.
Primary purpose: PREVENTION

Brief summary: RATIONALE: Green tea extract contains ingredients that may inhibit the growth of actinic keratosis.

PURPOSE: Randomized phase II trial to determine the effectiveness of green tea extract in treating patients who have actinic keratosis.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical and histopathologic regression of actinic keratoses
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: Frank L. Meyskens, MD, FACP
role: STUDY_CHAIR
References:
citation: Carpenter PM, Linden KG, McLaren CE, Li KT, Arain S, Barr RJ, Hite P, Sun JD, Meyskens FL Jr. Nuclear morphometry and molecular biomarkers of actinic keratosis, sun-damaged, and nonexposed skin. Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):1996-2002.
citation: Linden KG, Carpenter PM, McLaren CE, Barr RJ, Hite P, Sun JD, Li KT, Viner JL, Meyskens FL. Chemoprevention of nonmelanoma skin cancer: experience with a polyphenol from green tea. Recent Results Cancer Res. 2003;163:165-71; discussion 264-6. doi: 10.1007/978-3-642-55647-0_15.