Cervical Cancer, Cervical Intraepithelial Neoplasia Grade 1, Human Papilloma Virus Infection
Conditions
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.
Interventions
DRUGplacebo
Given orally
DIETARY_SUPPLEMENTdefined green tea catechin extract
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Polyphenon E | 50 |
| Placebo | 48 |
| Total | 98 |
Baseline characteristics
| Characteristic | Placebo | Polyphenon E | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 50 Participants | 98 Participants |
| Age, Continuous | 28.27 years STANDARD_DEVIATION 8.05 | 28.48 years STANDARD_DEVIATION 8.78 | 28.28 years STANDARD_DEVIATION 8.39 |
| Region of Enrollment United States | 48 participants | 50 participants | 98 participants |
| Sex: Female, Male Female | 48 Participants | 50 Participants | 98 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 50 | 34 / 48 |
| serious Total, serious adverse events | 0 / 50 | 1 / 48 |
Outcome results
Primary
Complete Response - Clearance of Oncogenic Human Papillomavirus (HPV) and Complete Colposcopic, Histologic and Cytologic Clearance of Disease
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polyphenon E | Complete Response - Clearance of Oncogenic Human Papillomavirus (HPV) and Complete Colposcopic, Histologic and Cytologic Clearance of Disease | 7 participants |
| Placebo | Complete Response - Clearance of Oncogenic Human Papillomavirus (HPV) and Complete Colposcopic, Histologic and Cytologic Clearance of Disease | 6 participants |
Primary
No Response - Persistent Oncogenic HPV Positivity, With or Without Evidence of Low Grade Cervical Intraepithelial Neoplasia
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polyphenon E | No Response - Persistent Oncogenic HPV Positivity, With or Without Evidence of Low Grade Cervical Intraepithelial Neoplasia | 27 participants |
| Placebo | No Response - Persistent Oncogenic HPV Positivity, With or Without Evidence of Low Grade Cervical Intraepithelial Neoplasia | 26 participants |
Primary
Partial Response - Clearance of Oncogenic HPV With Evidence of Low Grade Cervical Intraepithelial Neoplasia
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polyphenon E | Partial Response - Clearance of Oncogenic HPV With Evidence of Low Grade Cervical Intraepithelial Neoplasia | 1 participants |
| Placebo | Partial Response - Clearance of Oncogenic HPV With Evidence of Low Grade Cervical Intraepithelial Neoplasia | 6 participants |
Primary
Progression - Persistent Oncogenic HPV Positivity, With Evidence of Progression to Worsening Cervical Intraepithelial Neoplasia or Invasive Cancer
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polyphenon E | Progression - Persistent Oncogenic HPV Positivity, With Evidence of Progression to Worsening Cervical Intraepithelial Neoplasia or Invasive Cancer | 6 participants |
| Placebo | Progression - Persistent Oncogenic HPV Positivity, With Evidence of Progression to Worsening Cervical Intraepithelial Neoplasia or Invasive Cancer | 3 participants |