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)
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)
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
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.
Inclusion Criteria:
Meets criteria for 1 of the following groups:
Prospective group, meeting the following criteria:
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:
Historically persistent HPV-16-infection by PCR and HPV reverse transcription (RT)-PCR
No evidence of high-grade squamous intraepithelial lesions (HSIL) by colposcopy (Reid Index ≥ 6)
Reports no sex partner change since last index Pap screening test
Specimen-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:
Historically persistent HPV-16-infection by PCR and, where measurable, HPV RT-PCR showing no greater than 3-fold reduction over the index liquid-cytology specimen
No evidence of HSIL by colposcopy (Reid Index ≥ 6)
Menstrual period occurred at least once within the past 52 weeks
No HSIL by Pap test within the past year
Performance status - ECOG 0
No severe or unstable coagulation
Hepatitis B surface antigen negative
Hepatitis C antibody negative
No angina
No heart failure
No other cardiac condition
No respiratory condition
No asthma
No immunological disorders (e.g., lupus, diabetes, multiple sclerosis, or myasthenia gravis)
Not immunocompromised, suggestive of severe immune deficiency
HIV negative
No AIDS
No active infection, defined as fever > 100° F
No syphilis
No severe allergic reactions (anaphylactic response) to drugs or any other allergen
No history of allergy to any vaccine constituents, including cell- or tissue-system elements used to prepare the vaccine (e.g., bread products, yeast, or recombinant DNA technology using yeast systems)
Must agree to use effective form of contraception throughout vaccination period
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during vaccination period and for 5 months after study treatment
No sexual intercourse within 48 hours of virus specimen collection during study visits
No objects (e.g., tampons, douche, suppositories, fingers, or toes) within the vagina or rectum within 48 hours of virus specimen collection during study visits
No prior malignancy except nonmelanoma skin cancer
No medical or psychiatric illness than would preclude study participation or compliance
No other disorders requiring medical intervention that would preclude study participation
No prior HPV vaccine
More than 30 days since prior investigational vaccine
More than 30 days since prior systemic steroid therapy
No prior splenectomy
More than 30 days since prior investigational drug
More than 72 hours since prior antibiotic therapy for active infection