A Study of HPV Specific Immunotherapy in Subjects With HPV6 Associated Aerodigestive Precancerous Lesions and Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Injection site reactions including skin erythema, induration pain and tenderness at administration site
研究概览
简要总结
This is a Phase I, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3106 alone or in combination with INO-9012 DNA vaccines delivered by Electroporation to subjects with HPV6 associated aerodigestive precancerous lesions and malignancies.
详细描述
This is a Phase I, open-label, study to evaluate the safety, tolerability, and immunogenicity of 3 mg or 6 mg INO-3106 alone or in combination with 1 mg of INO-9012 (DNA plasmid encoding human interleukin 12) delivered by electroporation (EP) in subjects with HPV6 associated aerodigestive precancerous lesions and malignancies. Subjects will be enrolled in 2 cohorts (3 subjects in each cohort):
Cohort I: First 3 subjects will be enrolled sequentially and will receive INO-3106 alone or in combination with INO-9012.
Cohort II: The next 3 subjects will be treated with 6 mg of INO-3106 and 1 mg of INO-9012, or at the MTD (Maximum Tolerated Dose) determined in Cohort I.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated written Ethics Committee approved informed consent
- •Age ≥18 years
- •Histologically documented HPV-6 positive aerodigestive invasive malignancy (mucosal squamous cell head and neck cancer or lung cancer) who have completed therapies such as radiation/chemoradiation/chemotherapy; or
- •Histologically documented HPV-6 positive papilloma or HPV-6 related premalignant lesion (i.e., carcinoma in situ) in aerodigestive or head and neck regions.
- •Prior to study entry, subjects will have exhausted all treatments that are/have been used in these indications which may include any combination of surgery, anti-viral therapy, chemotherapy and/or radiation therapy.
- •Core biopsy must be obtained prior to enrollment to confirm invasive cancer. Archival material is allowed.
- •Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 cells/mm3, hemoglobin ≥ 9.0 g/dL, concentrations of total serum bilirubin within 1.5 x upper limit of normal (ULN), AST, ALT within 2.5x ULN, CPK within 2.5 x ULN, serum creatinine ≤ 1.5x ULN
- •ECOG (Eastern Cooperative Oncology Group) performance status of 0-2
排除标准
- •Participation in a clinical trial within 30 days before entry
- •Any cardiac pre-excitation syndromes, e.g. Wolff-Parkinson-White syndrome
- •Presence of metal implants within 5 cm of the planned site(s) of injection
- •Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids)
- •Administration of any vaccine within 6 weeks of enrollment
研究组 & 干预措施
Cohort I
3 mg of INO-3106 (D0); 6 mg of INO-3106 (Wk3); 6 mg of INO-3106 + 1 mg of INO-9012 (Wk6); 6 mg of INO-3106 + 1 mg of INO-9012 (Wk9);
干预措施: INO-3106, INO-9012 (Biological)
Cohort II
6 mg of INO-3106 in combination with 1 mg of INO-9012, or at the MTD determined above at D0, Wk3, Wk6, Wk9
干预措施: INO-3106, INO-9012 (Biological)
结局指标
主要结局
Injection site reactions including skin erythema, induration pain and tenderness at administration site
时间窗: Up to 15 weeks
Adverse events measured and graded in accordance with "Common Terminology Criteria for Adverse Events (CTCAE)", NCI version 4.03
时间窗: Up to 6 months
次要结局
- HPV6 specific Ig levels(Up to 6 months)
- Number of antigen-specific IFN-γ-secreting cells in response to stimulation with HPV6 by antigen-specific IFN-γ ELISpot assays(Up to 6 months)
- Cytotoxic T cells in response to HPV6 specific immunotherapy by flow cytometry(Up to 6 months)