Phase I Clinical Trial Assessing the Safety and Feasibility of Intramuscular pNGVL4aCRTE6E7L2 and TA-CIN Administration for the Treatment of Patients With Persistent HPV16+ ASC-US or LSIL
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Dose finding
研究概览
简要总结
Phase I clinical trial to assess safety of pNGVL4aCRTE6E7L2 DNA and TA-CIN protein vaccinations, and to seek the appropriate dose of the pNGVL4aCRTE6E7L2 DNA vaccine
详细描述
Primary Objectives
- To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL.
- To determine the appropriate intra-muscular injection dose of pNGVL4aCRTE6E7L2 DNA vaccine as determined by toxicity and immunogenicity for a subsequent phase II clinical trial.
- To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with persistent HPV16+ ASC-US/LSIL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with persistent (>6 month period) ASC-US/LSIL determined by cervical cytology at study entry (ThinPrep with imaging)
- •Patients whose cytologic samples are persistent (>6 month period) HPV16+ by Roche Cobas 4800, Roche Linear Array HPV Genotyping test or other FDA-approved HPV genotyping test at study entry. Co-infections with HPV types other than HPV16 are permissible for study entry.
- •Age ≥ 19 years
- •Baseline Eastern Cooperative Oncology Group
- •Patients must have adequate organ function at the time of enrollment as defined by the following parameters:
- •White blood cell count > 3,000
- •Absolute lymphocyte number > 500
- •Absolute neutrophil count > 1,000
- •Platelets > 90,000
- •Hemoglobulin > 9
- •Total bilirubin <3 X the institutional limit of normal
- •AST(SGOT)/ALT(SGPT) <3 X the institutional limit of normal
- •Creatinine < 2.5X the institutional limit of normal
- •Women of child-bearing potential must agree to use two forms of contraception (hormonal and barrier) prior to study entry and for 3 months after study completion.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Subject is able to adhere to the study visit schedule and other protocol requirements.
排除标准
- •Patients with ASC-US/LSIL determined by cervical cytology at study entry that are HPV16 negative.
- •Histologic evidence of CIN2+
- •Patients with a diagnosis of immunosuppression or prolonged, active use of immunosuppressive medications such as steroids.
- •Prior vaccination with any HPV antigen (prophylactic or therapeutic).
- •Patients who are receiving any other investigational agents within 28 days prior to the first dose.
- •Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients with a history of autoimmune disease such as multiple sclerosis, exclusive of a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease.
- •Patients with a history of allergic reactions attributed to compounds used in agent preparation.
- •Patients who are pregnant or breast feeding.
- •Patient with active or chronic infection of HIV, HCV, or HBV.
- •Patients who have had a prior LEEP or cervical conization procedure.
- •History of prior malignancy permitted if patient has been disease free for ≥ 5 years; however individuals with completely resected basal cell or squamous cell carcinoma of the skin within this interval may be enrolled.
- •Inability to understand or unwillingness to sign an informed consent document.
研究组 & 干预措施
pNGVL4aCRTE6E7L2 1 mg dose
Intermediate dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
干预措施: pNGVL4aCRTE6E7L2 (Biological)
pNGVL4aCRTE6E7L2 0.3mg dose
Low dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
干预措施: pNGVL4aCRTE6E7L2 (Biological)
PVX-6
Selected dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0 and 4, and the TA-CIN protein is administered by intramuscular injection at week 8.
干预措施: pNGVL4aCRTE6E7L2 (Biological)
pNGVL4aCRTE6E7L2 3 mg dose
High dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
干预措施: pNGVL4aCRTE6E7L2 (Biological)
PVX-6
Selected dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0 and 4, and the TA-CIN protein is administered by intramuscular injection at week 8.
干预措施: TA-CIN (Biological)
结局指标
主要结局
Dose finding
时间窗: 12 months
To determine the appropriate intra-muscular injection dose of pNGVL4aCRTE6E7L2 DNA vaccine as determined by toxicity and immunogenicity for a subsequent phase II clinical trial
Safety and feasibility of pNGVL4aCRTE6E7L2 DNA vaccination
时间窗: 12 months
To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL
Safety and feasibility of PVX-6 vaccination
时间窗: 12 months
To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with persistent HPV16+ ASC-US/LSIL
次要结局
- HPV16 CD8 T cell response(12 months)
- HPV16 L2E7E6 T cell proliferative response(12 months)
- Cytologic clearance(12 months)
- HPV16 antibody response(12 months)
- Clearance of HPV16(12 months)
研究者
Rebecca Arend
Professor of Medicine, Division Director Gynecology Oncology
University of Alabama at Birmingham