Vaccine Therapy in Preventing Cervical Cancer in Patients With Cervical Intraepithelial Neoplasia

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)

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.

cervical cancer, cervical intraepithelial neoplasia grade 2, cervical intraepithelial neoplasia grade 3

3-500mcg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals. Genetic (recombinant DNA vaccine)

3-1mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine)

3-3mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine)

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.

Number of participants whose t-cell immune responses correlated with histologic regression of disease or viral clearance of HPV

Number of participants whose T-cell immune responses correlated with the immune responses observed in the preclinical model

DISEASE CHARACTERISTICS: Histologically confirmed cervical intraepithelial neoplasia (CIN2/3) Human papillomavirus-16-positive disease PATIENT CHARACTERISTICS: - Age: > 18 Other Not pregnant Immunocompetent

Trimble CL, Peng S, Kos F, Gravitt P, Viscidi R, Sugar E, Pardoll D, Wu TC. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res. 2009 Jan 1;15(1):361-7. doi: 10.1158/1078-0432.CCR-08-1725.