An Exploratory Study to Evaluate the Effect of HPV 16 Vaccine on the Reduction of Viral Load in HPV 16 Positive Women With Persistent Viral Infection, But Low Grade Disease (ASCUS/LSIL)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Atypical Squamous Cells of Undetermined Significance
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 139
- Locations
- 1
- Primary Endpoint
- HPV-16 viral load
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This randomized phase II trial is studying how well SGN-00101 vaccine works compared to a placebo in treating human papillomavirus and preventing cervical cancer in patients with abnormal cervical cells. Vaccines, such as SGN-00101, may make the body build an immune response to kill human papillomavirus and abnormal cervical cells and may be effective in preventing cervical cancer
Detailed Description
PRIMARY OBJECTIVES: I. Compare the effectiveness of SGN-00101 vaccine vs placebo in reducing the human papillomavirus (HPV)-16 viral load in patients with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) of the cervix with persistent HPV-16 infection who are at increased risk for developing a high-grade squamous intraepithelial lesion or invasive cervical cancer. II. Compare the natural history of HPV-16 viral load in patients treated with these regimens. III. Compare the effect of HPV-16 variants on viral load response in patients treated with these regimens. IV. Compare the relative effectiveness of these regimens on the regression of cervical cellular atypias (based on Pap test results), in terms of the regression of cytologic findings of LSIL and ASCUS to normal findings and resolution or regression of colposcopically defined cervicovaginal lesions, in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive SGN-00101 vaccine subcutaneously (SC) on day 1 of weeks 1, 4, and 8 for a maximum of 3 injections in the absence of unacceptable toxicity or the development of an invasive malignancy or serious illness. ARM II: Patients receive placebo vaccine SC on day 1 of weeks 1, 4, and 8 for a maximum of 3 injections in the absence of unacceptable toxicity or the development of an invasive malignancy or serious illness. Patients are followed at 12, 24, and 52 weeks after the last vaccination.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Meets criteria for 1 of the following groups:
- •Prospective group, meeting the following criteria:
- •Evidence of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) by Pap test
- •Human papillomavirus (HPV)-16-positive by polymerase chain reaction (PCR) and PGMY09/PGMY11 oligonucleotide primers viral load assay
- •Medical records-based group, meeting the following criteria:
- •Medical-record evidence of ASCUS or LSIL by Pap test within the past 6-12 months
- •Meets 1 of the following criteria:
- •Liquid-cytology findings of ASCUS or LSIL
- •Colposcopic evidence of a LSIL by the Reid Index score of 1-5
- •Historically persistent HPV-16-infection by PCR and HPV reverse transcription (RT)-PCR
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
HPV-16 viral load
Time Frame: 6 months
Following the univariate modeling, multivariate logistic regression models will be constructed by adding the demographic factors, baseline viral load, and type of cellular atypia to the model. The univariate logistic regression model for infection resolution is equivalent to a chi-square test.
Natural history of HPV 16 viral load
Time Frame: 6 months
A repeated measures version of the zero-inflated log-normal model will be constructed.
Regression or non-regression of the cellular atypia
Time Frame: Up to 52 weeks
The analysis for this will employ logistic regression models. A multivariate logistic regression model will be constructed. . A two group continuity corrected chi squared test with a 0.050 two-sided significance level will be used.
Secondary Outcomes
- HPV-16 viral load(3 months)
- Time to infection resolution(Up to 52 weeks)
- Time to disease resolution(Up to 52 weeks)