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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

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

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

Study type: Interventional

Funder types: NIH

Identifiers

NCT00303823

NCI-2009-00893 (Registry Identifier)

05-0144-01 (Other Identifier)

P30CA023074 (U.S. NIH Grant/Contract)

CDR0000458081

HSC 05-40

N01CN35158 (U.S. NIH Grant/Contract)

UAZ03-1-02 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 98 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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98 participants in 2 patient groups, including a placebo group

Arm I

Experimental group

Description:

Patients receive oral green tea extract once daily for 16 weeks in the absence of unacceptable toxicity.

Treatment:

Other: laboratory biomarker analysis

Dietary Supplement: defined green tea catechin extract

Arm II

Placebo Comparator group

Description:

Patients receive oral placebo once daily for 16 weeks in the absence of unacceptable toxicity.

Treatment:

Other: laboratory biomarker analysis

Drug: placebo