Clinical trial NCT00303823: Green Tea Extract in Preventing Cervical Cancer in Patients With Human Papillomavirus and Low-Grade Cervical Intraepithelial Neoplasia
Official title: A Phase II Trial of Polyphenon E for Cervical Cancer Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Cervical Intraepithelial Neoplasia Grade 1
Human Papilloma Virus Infection
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-03-17
Enrollment: 98
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Complete Response - Clearance of Oncogenic Human Papillomavirus (HPV) and Complete Colposcopic, Histologic and Cytologic Clearance of Disease
timeFrame: 4 months
measure: Partial Response - Clearance of Oncogenic HPV With Evidence of Low Grade Cervical Intraepithelial Neoplasia
timeFrame: 4 months
measure: No Response - Persistent Oncogenic HPV Positivity, With or Without Evidence of Low Grade Cervical Intraepithelial Neoplasia
timeFrame: 4 months
measure: Progression - Persistent Oncogenic HPV Positivity, With Evidence of Progression to Worsening Cervical Intraepithelial Neoplasia or Invasive Cancer
timeFrame: 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center - Tucson
state: Arizona
Study officials:
affiliation: Arizona Cancer Center - Tucson
name: Francisco Garcia
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.