Clinical Protocol for Wild Type p53 Gene Induction in Premalignancies of Squamous Epithelium of the Oral Cavity and Oral Pharynx Via an Adenoviral Vector [NCI Supplied Agent Ad-p53, (INGN 201) (Advexin®) NSC 683550, IND# 7135]
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 2
- 主要终点
- Frequency of adverse events
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of gene therapy and to see how well it works in preventing cancer in patients with premalignant carcinoma of the oral cavity or pharynx. Inserting the p53 gene into a person's tumor cells may improve the body's ability to kill the tumor cells
详细描述
OBJECTIVES:
I. Determine the acute toxic effects of Ad5CMV-p53 gene administered as an oral rinse and as an intramucosal injection in patients with diffuse premalignant carcinoma of the oral cavity or oral pharynx.
II. Determine the maximum tolerated dose of this drug in these patients. III. Determine the topical transduction efficiency of adenoviral-mediated wild type p53 gene transfer in patients treated with this drug.
IV. Determine the efficacy of this drug in reversing the histology of oral premalignancies in these patients.
V. Determine the distribution of transgenic protein within the area of the premalignant lesion in patients treated with this drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Histologically confirmed mild to moderate dysplasia OR severe dysplasia/carcinoma in situ of the oral cavity or oral pharynx
- •Clinically evident diffuse premalignant disease, defined by 1 of the following mucosal abnormalities:
- •Extension between adjacent organ structures (e.g., lateral tongue, ventral tongue, and the floor of the mouth)
- •Extensive surface area, including the entire ventral tongue or floor of the mouth or buccal mucosa, in a velvety "indiscreet" pattern
- •Meets 1 of the following criteria:
- •Previously treated with conventional treatment (e.g., radiotherapy or surgery) for a prior head and neck malignancy
- •Failed biochemoprevention approaches for premalignant disease
- •Failed other therapeutic approaches for premalignant disease
- •No active squamous cell carcinoma of the head and neck
- •Performance status - Karnofsky 70-100%
- •Absolute granulocyte count at least 2,000/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 1.0 mg/dL
- •Creatinine no greater than 1.5 mg/dL
- •No hypertension (baseline blood pressure 140/90 mm Hg or higher)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception during and for 1 year after study participation
- •HIV-1 negative
- •No known contact with former tissue or organ transplantation recipients or individuals with severe immunodeficiency disease (acquired or congenital) during and for 28 days after study treatment
- •No prior malignancy within the past 2 years except nonmelanoma skin cancer or aerodigestive cancer
- •No active systemic viral, bacterial, or fungal infections requiring treatment
- •No serious concurrent illness that would preclude study compliance and follow-up
- •No psychological, familial, sociological, geographical, or other condition that would preclude study compliance and follow-up
- •See Disease Characteristics
- •More than 21 days since prior chemotherapy (42 days for mitomycin and nitrosoureas)
- •No concurrent systemic chemotherapy
- •No concurrent prednisone or the equivalent, including corticosteroids of more than 10 mg/day
- •See Disease Characteristics
- •More than 3 months since prior radiotherapy involving the lesion selected for this study
- •No concurrent radiotherapy
- •See Disease Characteristics
- •More than 8 weeks since prior investigational agents
- •No prior experimental therapy (i.e., oral, systemic, topical, or direct injection) for the lesion selected for treatment in this study
- •No other concurrent immunosuppressive therapy
- •No other concurrent investigational agents
- •No concurrent aspirin dose greater than 175 mg/day
排除标准
- 未提供
结局指标
主要结局
Frequency of adverse events
时间窗: Up to 15 years
Severity of adverse events graded using the CTCAE version 3.0
时间窗: Up to 15 years
Maximum tolerated dose of Ad5CMV-p53 gene
时间窗: 6 months
Evaluated by the frequency and relationship of dose-limiting toxicities, if any, experienced by patients during dose escalation.
Pharmacodynamics evaluated by examining the injected precancerous lesion for induction of apoptosis and expression of the p53 protein
时间窗: 168 days
Presented using descriptive statistics, frequency tabulations, and graphical displays over time by treatment cohort.
次要结局
未报告次要终点