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

Phase 2

Completed

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

Interventions: Dietary Supplement: defined green tea catechin extract
Drug: placebo
Other: laboratory biomarker analysis

Registration Number: NCT00303823

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 98

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	laboratory biomarker analysis	Patients receive oral green tea extract once daily for 16 weeks in the absence of unacceptable toxicity.
Arm II	laboratory biomarker analysis	Patients receive oral placebo once daily for 16 weeks in the absence of unacceptable toxicity.
Arm I	defined green tea catechin extract	Patients receive oral green tea extract once daily for 16 weeks in the absence of unacceptable toxicity.
Arm II	placebo	Patients receive oral placebo once daily for 16 weeks in the absence of unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
No Response - Persistent Oncogenic HPV Positivity, With or Without Evidence of Low Grade Cervical Intraepithelial Neoplasia	4 months
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
Progression - Persistent Oncogenic HPV Positivity, With Evidence of Progression to Worsening Cervical Intraepithelial Neoplasia or Invasive Cancer	4 months

Secondary Outcome Measures