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)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Safety and tolerability as determined by number of participants with Serious Adverse Events
研究概览
简要总结
RATIONALE: Vaccines made from DNA or a gene-modified virus may help the body build an effective immune response to kill tumor cells. Biological therapies, such as imiquimod, may stimulate the immune system in different ways and stop tumor cells from growing. Applying topical imiquimod to the cervix may be an effective treatment for cervical intraepithelial neoplasia. Giving vaccine therapy together with imiquimod may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy and to see how well it works when given with or without imiquimod in treating patients with grade 3 cervical intraepithelial neoplasia.
详细描述
OBJECTIVES:
Primary
- 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).
Secondary
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Groups 1-3
Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine intramuscularly (IM) on days 1 and 29 and TA-HPV vaccine IM on day 57.
干预措施: TA-HPV (Biological)
Groups 1-3
Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine intramuscularly (IM) on days 1 and 29 and TA-HPV vaccine IM on day 57.
干预措施: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine (Biological)
Group 4
Patients receive topical imiquimod on days 1, 29, and 57.
干预措施: imiquimod (Drug)
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.
干预措施: TA-HPV (Biological)
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.
干预措施: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine (Biological)
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.
干预措施: imiquimod (Drug)
结局指标
主要结局
Safety and tolerability as determined by number of participants with Serious Adverse Events
时间窗: 10 weeks from the first intervention
Presence of Serious Adverse Events (as defined by according to NCI CTCAE v3.0) or dose limiting toxicities related to the study drugs.
次要结局
- Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 15(15 weeks from the date of the first intervention)
- Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 28(28 weeks from the date of the first intervention)
- Quantitative changes in cervical HPV viral load in exfoliated cell samples(41 weeks from the date of the first intervention)
- Change in number of lesions by serial digital colposcopy from week 0 to week 15(Change from baseline to 15 weeks)
- Characterization of peripheral and local tissue response to vaccination(41 weeks)
- Correlation between measures of immune response and preclinical experimental data(41 weeks from the date of the first study intervention)
- Change in size of lesions by serial digital colposcopy from week 0 to week 15(Change from baseline to 15 weeks)
- Correlation of immune response with clinical response(41 weeks)