Phase I Study Photodynamic Therapy Using Lutrin (Lutetium Texaphyrin) in the Treatment of Patients With Cervical Intraepithelial Neoplasia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1)
研究概览
简要总结
Phase I trial to study the effectiveness of photodynamic therapy with lutetium texaphyrin in treating patients who have cervical intraepithelial neoplasia. Photodynamic therapy uses light and drugs such as lutetium texaphyrin that make abnormal cells more sensitive to light and may kill abnormal cells in the cervix and prevent the development of cervical cancer
详细描述
OBJECTIVES:
I. Determine the optimal dosage with the least toxicity of lutetium texaphyrin as well as the length of time following its systemic injection that provides the maximum differential in drug uptake between the target dysplastic squamous cells and normal squamous epithelium when given to patients with cervical intraepithelial neoplasia (CIN).
II. Determine, by histomorphometry, the photodynamic light dose that demonstrates the greatest treatment selectivity between normal cervical epithelium and CIN with the least amount of cervical pain and necrosis.
OUTLINE: This is a dose-escalation study of lutetium texaphyrin (part 1) followed by a dose-escalation study of light fluence (part 2).
Part 1: Patients receive lutetium texaphyrin IV over 5-20 minutes. Patients undergo in vivo tissue assessment by spectrometer at 0, 1, 3, 5, 12, and 24 hours and loop electrical excision procedure (LEEP) at 24 hours after lutetium texaphyrin infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Cervical intraepithelial neoplasia (CIN) grade II or III
- •No cytologic, colposcopic, or histologic evidence of invasive squamous cell carcinoma
- •No evidence of glandular atypia on Pap smear, endocervical curettage, or biopsy
- •No inadequate colposcopy (i.e., entire transformation zone cannot be visualized and/or upper limit of a colposcopically abnormal lesion cannot be visualized fully)
- •HIV positive but not currently on antiviral therapy
- •Performance status - 0-2
- •WBC greater than 4,000/mm^3
- •Absolute neutrophil count greater than 2,000/mm^3
- •Platelet count normal
- •Liver enzymes normal
- •No liver impairment
- •BUN normal
- •Creatinine normal
- •No renal insufficiency
- •No coronary artery disease
- •No cardiac arrhythmia
- •No congestive heart failure
- •Not pregnant or nursing
- •Fertile patients must use effective contraception during and for at least 1 month after study
- •No other serious medical illness (e.g., non-insulin and insulin-dependent diabetes or connective tissue disorders)
- •No other prior or concurrent malignancy
- •No known G6PD deficiency
- •No porphyria
- •No history of 2 prior ablative/excisional therapies (i.e., cryotherapy, laser ablation, loop electrical excision procedure, or cold knife cone biopsy)
- •No concurrent non-steroidal anti-inflammatory drugs (NSAIDS)
- •No other concurrent significant medication/therapy such as:
- •Anti-hypertensives, anti-arrhythmics, or inotropic agents for cardiopulmonary disease
- •Diuretics for renal insufficiency
- •Steroids or NSAIDs for connective tissue disorders
排除标准
- 未提供
研究组 & 干预措施
Part 1 (lutetium texaphyrin, LEEP)
Patients receive lutetium texaphyrin IV over 5-20 minutes. Patients undergo in vivo tissue assessment by spectrometer at 0, 1, 3, 5, 12, and 24 hours and loop electrical excision procedure (LEEP) at 24 hours after lutetium texaphyrin infusion.
干预措施: motexafin lutetium (Drug)
Part 1 (lutetium texaphyrin, LEEP)
Patients receive lutetium texaphyrin IV over 5-20 minutes. Patients undergo in vivo tissue assessment by spectrometer at 0, 1, 3, 5, 12, and 24 hours and loop electrical excision procedure (LEEP) at 24 hours after lutetium texaphyrin infusion.
干预措施: loop electrosurgical excision procedure (Procedure)
Part 1 (lutetium texaphyrin, LEEP)
Patients receive lutetium texaphyrin IV over 5-20 minutes. Patients undergo in vivo tissue assessment by spectrometer at 0, 1, 3, 5, 12, and 24 hours and loop electrical excision procedure (LEEP) at 24 hours after lutetium texaphyrin infusion.
干预措施: laboratory biomarker analysis (Other)
Part 2 (lutetium texaphyrin, laser therapy, LEEP)
Patients receive lutetium texaphyrin IV over 5-20 minutes. A laser delivers 730 nm of light to the cervix for 4, 8, or 16 minutes. Patients undergo LEEP at 4, 8, or 12 hours after exposure of the cervix to the light source.
干预措施: motexafin lutetium (Drug)
Part 2 (lutetium texaphyrin, laser therapy, LEEP)
Patients receive lutetium texaphyrin IV over 5-20 minutes. A laser delivers 730 nm of light to the cervix for 4, 8, or 16 minutes. Patients undergo LEEP at 4, 8, or 12 hours after exposure of the cervix to the light source.
干预措施: photodynamic therapy (Drug)
Part 2 (lutetium texaphyrin, laser therapy, LEEP)
Patients receive lutetium texaphyrin IV over 5-20 minutes. A laser delivers 730 nm of light to the cervix for 4, 8, or 16 minutes. Patients undergo LEEP at 4, 8, or 12 hours after exposure of the cervix to the light source.
干预措施: loop electrosurgical excision procedure (Procedure)
Part 2 (lutetium texaphyrin, laser therapy, LEEP)
Patients receive lutetium texaphyrin IV over 5-20 minutes. A laser delivers 730 nm of light to the cervix for 4, 8, or 16 minutes. Patients undergo LEEP at 4, 8, or 12 hours after exposure of the cervix to the light source.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1)
时间窗: Up to 24 hours
A simplified graphical analysis will be utilized to determine the drug dose and time after administration that provides the largest differential area between lutein texaphyrin tissue levels in neoplastic and normal cervical tissue
Maximal differential in Lutrin tissue levels between normal and dysplastic cells (Part 1)
时间窗: At the time of LEEP
Percentage of tissue demonstrating PDT related effects (apoptosis/ necrosis) for normal versus abnormal epithelium at each total fluence for each LEEP cone biopsy specimen
时间窗: At LEEP time
A simplified graphical analysis will be utilized to determine the fluence that provides the maximal differential area between neoplastic and normal cervical epithelium and stroma.
次要结局
未报告次要终点