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

A Phase II Trial of Polyphenon E for Cervical Cancer Prevention

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Human Papilloma Virus Infection; Cervical Intraepithelial Neoplasia Grade 1
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: placebo; Dietary supplement: defined green tea catechin extract

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center - Tucson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Francisco Garcia, Arizona Cancer Center - Tucson

Publications and helpful links

General Publications

• Garcia FA, Cornelison T, Nuno T, Greenspan DL, Byron JW, Hsu CH, Alberts DS, Chow HH. Results of a phase II randomized, double-blind, placebo-controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia. Gynecol Oncol. 2014 Feb;132(2):377-82. doi: 10.1016/j.ygyno.2013.12.034. Epub 2014 Jan 2.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: March 15, 2006
• First Submitted That Met QC Criteria: March 15, 2006
• First Posted (Estimate): March 17, 2006

Study Record Updates

• Last Update Posted (Estimate): May 5, 2015
• Last Update Submitted That Met QC Criteria: April 14, 2015
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; DNA Virus Infections; Tumor Virus Infections; Neoplasms, Squamous Cell; Neoplasms; Uterine Cervical Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Papillomavirus Infections; Papilloma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Epigallocatechin gallate
• Other Study ID Numbers: NCI-2009-00893 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA023074 (U.S. NIH Grant/Contract); N01CN35158 (U.S. NIH Grant/Contract); CDR0000458081; HSC 05-40; 05-0144-01 (Other Identifier: Arizona Cancer Center - Tucson); UAZ03-1-02 (Other Identifier: DCP)