Green Tea Extract in Preventing Cervical Cancer in Patients With Human Papillomavirus and Low-Grade Cervical Intraepithelial Neoplasia

Study Overview
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Brief Summary
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This randomized phase II trial is studying green tea extract to see how well it works compared to a placebo in preventing cervical cancer in patients with human papillomavirus and low-grade cervical intraepithelial neoplasia. Chemoprevention is the use of certain substances to keep cancer from forming, growing, or coming back. The use of green tea extract may stop cervical cancer from forming in patients with human papillomavirus and low-grade cervical intraepithelial neoplasia. It is not yet known whether green tea extract is more effective than a placebo in preventing cervical cancer in patients with human papillomavirus and low-grade cervical intraepithelial neoplasia.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the effect of green tea extract (Polyphenon E®) in patients with human papillomavirus (HPV) expression and low-grade cervical intraepithelial neoplasia (CIN 1) in a pre- and post-treatment setting. SECONDARY OBJECTIVES: I. Compare the toxicity of green tea extract vs placebo among patients with CIN 1. TERTIARY OBJECTIVES: I. Evaluate the utility of karyometry as an intermediate endpoint biomarker for cervical chemoprevention studies. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral green tea extract (Polyphenon E®) once daily for 16 weeks in the absence of unacceptable toxicity. ARM II: Patients receive oral placebo once daily for 16 weeks in the absence of unacceptable toxicity. After completion of study treatment, patients are followed for 2 weeks.

Official Title
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A Phase II Trial of Polyphenon E for Cervical Cancer Prevention

Conditions
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Cervical Cancer, Cervical Intraepithelial Neoplasia Grade 1, Human Papilloma Virus Infection

Intervention / Treatment
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* Drug: placebo
* Dietary Supplement: defined green tea catechin extract
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed cervical intraepithelial neoplasia 1 (CIN 1) AND oncogenic human papillomavirus (HPV) positivity At increased risk for developing cervical cancer due to >= 1 of the following criteria (documented 6-12 months ago)*: Positive oncogenic HPV on DNA hybrid capture Low-grade squamous intraepithelial lesion cytology Histopathologically documented CIN 1 on cervical biopsy [Note: *Patients must now have current CIN 1 by histology or colposcopy AND HPV positivity] Cervical dysplasia by colposcopy OR positive biopsy No invasive cervical cancer or high-grade intraepithelial neoplasia on cervical biopsy or endocervical curettage ECOG performance status < 2 Total bilirubin < 2 times upper limit of normal (ULN) AST < 2 times ULN ALT normal Creatinine < 2.0 mg/dL Able and willing to return to clinic for study visits once every 4 weeks for the duration of the study No history of allergic reaction to tea or related dietary products No HIV positive patients (or AIDS/HIV-associated complex) No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection other than HPV Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness/social situation that would limit compliance with study requirements No history of any cancer except nonmelanoma skin cancer Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No regular intake of 6 or more servings of tea per week within 1 month prior to study entry No treatment for genital condyloma within 30 days prior to study entry No prior pelvic irradiation No concurrent tea (green, black, or oolong) or tea-derived products No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral green tea extract once daily for 16 weeks in the absence of unacceptable toxicity. | Dietary Supplement: defined green tea catechin extract<br>* Given orally<br>* Other names: Polyphenon E;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Placebo Comparator: Arm II<br>Patients receive oral placebo once daily for 16 weeks in the absence of unacceptable toxicity. | Drug: placebo<br>* Given orally<br>* Other names: PLCB;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response - Clearance of Oncogenic Human Papillomavirus (HPV) and Complete Colposcopic, Histologic and Cytologic Clearance of Disease |  | 4 months | 
| Partial Response - Clearance of Oncogenic HPV With Evidence of Low Grade Cervical Intraepithelial Neoplasia |  | 4 months | 
| No Response - Persistent Oncogenic HPV Positivity, With or Without Evidence of Low Grade Cervical Intraepithelial Neoplasia |  | 4 months | 
| Progression - Persistent Oncogenic HPV Positivity, With Evidence of Progression to Worsening Cervical Intraepithelial Neoplasia or Invasive Cancer |  | 4 months |