RATIONALE: Vaccines made from protein and DNA may help the body build an effective immune response to kill abnormal cells in the cervix. The use of vaccine therapy may prevent cervical cancer. PURPOSE: This phase I/II trial is studying the side effects and best dose of vaccine therapy and to see how well it works in preventing cervical cancer in patients with cervical intraepithelial neoplasia and human papillomavirus.
OBJECTIVES: Primary * Determine the feasibility and toxicity of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine in preventing cervical cancer in patients with human papillomavirus (HPV)-16-positive grade 2 or 3 cervical intraepithelial neoplasia. * Determine the effect of this vaccine on the histology of cervical tissue specimens from these patients. Secondary * Determine changes in lesion size and HPV viral load in patients treated with this vaccine. * Determine the cellular, humoral, and local tissue immune responses in patients treated with this vaccine. * Correlate measures of immune response with clinical response in patients treated with this vaccine. * Correlate measures of immune response in patients treated with this vaccine with those observed in the preclinical model. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. * Phase I: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine subcutaneously once in weeks 0, 4, and 8 in the absence of disease progression or unacceptable toxicity. Patients undergo colposcopy in week 8, 15 and 19 and a therapeutic loop electrosurgical excision procedure (LEEP) in week 15. Cohorts of patients receive escalating doses of vaccine until the safest dose is determined. * Phase II: Patients receive vaccine as in phase I but at the safest dose determined in phase I. Patients also undergo colposcopy and LEEP as in phase I. After completion of the study treatment, patients are followed annually for 15 years. PROJECTED ACCRUAL: Approximately 150 patients (approximately 12 will be treated in phase I and 25 will be treated in phase II) will be accrued for this study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
recombinant DNA vaccine
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Safety and Toxicity
Number of participants with serious adverse events (SAE) according to CTCAE 3.0 grading.
Time frame: for the duration of the study, and whenever possible, for an additional 5 years
Efficacy
The efficacy of pNGVL4a-SigE7(detox)HSP70 DNA vaccine, administered intra-muscularly. This is reported as number of participants with histologic regression of CIN2/3 to CIN1 or less by colposcopically-directed biopsy.
Time frame: for the duration of the study, and whenever possible, for an additional 5 years
Regression of CIN3 Lesions
Number of participants with absence of CIN3 lesions at week 15
Time frame: 15 weeks
Number of Participants With T-cell Immune Responses in the Blood
Systemic T-cell response as measured by γ-INF enzyme-linked immunospot assays (ELISpot)
Time frame: 41 weeks
Number of Participants With Correlated Measures of Immune Response With Clinical Response
Number of participants whose t-cell immune responses correlated with histologic regression of disease or viral clearance of HPV
Time frame: 9 months
Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model
Number of participants whose T-cell immune responses correlated with the immune responses observed in the preclinical model
Time frame: 9 months
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NONE
Enrollment
16