A Phase I/II Clinical Trial of pNGVL4a-Sig/E7 (Detox)/HSP70 for the Treatment of Patients With HPV 16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)
- 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
- Determine changes in lesion size and HPV viral load in patients treated with this
- 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
- 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Prevention
Cornelia L. Trimble, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|