A Phase I Efficacy and Safety Study of HPV16-specific Therapeutic DNA-vaccinia Vaccination in Combination With Topical Imiquimod, in Patients With HPV16+ High Grade Cervical Dysplasia (CIN3)
- To evaluate safety, tolerability, and feasibility of pNGVL4a-Sig/E7(detox)/HSP70 DNA
vaccine and TA-HPV vaccine with or without imiquimod in patients with human
papillomavirus (HPV)16-positive grade 3 cervical intraepithelial neoplasia (CIN3).
- To evaluate the effect of this regimen on histology, based on the regression of
cervical intraepithelial neoplasia.
- To evaluate the feasibility and safety of study immunotherapy in these patients.
- To evaluate the quantitative changes in cervical HPV viral load in these patients
following study immunotherapy.
- To evaluate changes in lesion size.
- To evaluate the cellular and humoral immune response to vaccination.
- To evaluate local tissue immune response.
- To correlate measures of immune response with clinical response.
- To correlate measures of immune response with those observed in the preclinical model.
- To evaluate if the efficacy of the prime-boost vaccination can be improved with the
cervical application of imiquimod.
OUTLINE: This is a dose escalation study of TA-HPV vaccine (groups 1-3 only). Patients are
assigned to 1 of 5 treatment groups.
- Groups 1-3: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine intramuscularly
(IM) in weeks 0 and 4 and TA-HPV vaccine IM in week 8.
- Group 4: Patients receive topical imiquimod applied to the cervix once in weeks 0, 4,
- Group 5: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV vaccine as
in groups 1-3, and imiquimod as in group 4.
Patients experiencing no improvement of their lesions at week 15 undergo standard cone
resection of the squamocolumnar junction. If there is either 1) regression of the size of
the lesions by colposcopy and/or 2) no CIN3 lesions detected by colposcopy/biopsy and Pap
smear and/or 3) significant decrease of HPV viral load, patients are followed until week 28.
At that time, loop electrosurgical excision procedure (LEEP) resection is performed if there
is a CIN3 lesion detected by colposcopy/biopsy or suspected by Pap smear. Patients
undergoing LEEP are followed until week 32. Patients not undergoing LEEP are followed until
week 41 to confirm CIN3 regression.
Blood and tissue samples are collected periodically to measure immune response via ELISA,
determine viral load and identify co-infecting HPV types via reverse-line blotting, and
analyze lymphocytes via flow cytometry.
PROJECTED ACCRUAL: A total of 36 patients (3 in groups 1 and 2, 12 in groups 3 and 5, and 6
in group 4) will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety (according to NCI CTCAE v3.0) and tolerability
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|