A Combined Phase I/II Single Site Study to Determine the Safety and Efficacy of Photodynamic Therapy (PDT) Utilizing 5-aminolevulinic Acid (5-ALA) and PDT in the Treatment of Premalignant Oral and/or Oropharynx Lesions.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- The Objective Response Rate is the Number of Participants With Significant Response (SR), Partial Response (PR) or No Response (NR).
研究概览
简要总结
Oral leukoplakia within the mouth is a visible white patch which can develop into cancer if not treated. There is no good treatment for these lesions, apart from surgery which is associated with significant side effects and physical deformation of the treated area.
The investigators hypothesized that photodynamic therapy can be used safely and effectively to induce significant regression of oral leukoplakia.
详细描述
This is a combined Phase I/II non-randomized prospective study designed to determine the safety and assess the clinical efficacy of PDT in the treatment of oral leukeplekia with 5-ALA and 585-nm PDL with 1.5 ms pulse time. In the first part of the study we determined the maximum tolerated dose (MTD) of the PDL radiant exposure in combination with 5-ALA. In the second phase of the study, this dose is used to treat subjects at the MTD in order to determine the efficacy of the treatment by documenting the regression of the treated lesions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least one grossly visible premalignant lesion (i.e. leukoplakia or erythroplakia) in the oral cavity or oropharynx, with a confirmed diagnosis of leukoplakia with or without dysplasia,measuring ≥ 10 mm in diameter.
- •Informed of alternative treatment methods including watchful waiting, laser ablation, or surgical resection.
- •Eligible for long-term follow-up for at least one year and be able to tolerate biopsies.
- •Subject has signed an informed consent.
- •Subject is between the ages of 18 - 80 years of age.
- •Male or Female
- •Zubrod performance status of 0 or 1 at screening. See Appendix A
排除标准
- •Known sensitivity to porphyrins or photoactive medications - See Appendix B
- •Invasive carcinoma of the lesion as demonstrated by biopsy.
- •Subjects with inherited or acquired blood clotting defects
- •Women who are breast feeding, have a positive (+) urine pregnancy test, or refuse to use 2 effective means of contraception during drug exposure and up to 48 hours after.
- •Subjects with porphyria
- •Life expectancy less than 12 months
- •Inability or unwillingness of subject to give written informed consent
研究组 & 干预措施
Phase 1 light dose escalation
During Phase I, to determine the maximum tolerated energy density of the Pulse Dye Laser operated at 585 nm with a pulse time of 1.5 ms (PDL-585), when used in combination with 5-aminolevulinic acid (5-ALA) applied topically to the premalignant lesion.
The maximum tolerated energy density will be called the Maximum Tolerated Dose (MTD). Procedure: Fluorescence Diagnosis Imaging Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 6, 7 and 8 J/cm2.
干预措施: PDL-585, ScleroPLUS laser (Device)
Phase 1 light dose escalation
During Phase I, to determine the maximum tolerated energy density of the Pulse Dye Laser operated at 585 nm with a pulse time of 1.5 ms (PDL-585), when used in combination with 5-aminolevulinic acid (5-ALA) applied topically to the premalignant lesion.
The maximum tolerated energy density will be called the Maximum Tolerated Dose (MTD). Procedure: Fluorescence Diagnosis Imaging Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 6, 7 and 8 J/cm2.
干预措施: 5-Aminolevulinic Acid (Levulan KerastickTM) (Drug)
Phase 1 light dose escalation
During Phase I, to determine the maximum tolerated energy density of the Pulse Dye Laser operated at 585 nm with a pulse time of 1.5 ms (PDL-585), when used in combination with 5-aminolevulinic acid (5-ALA) applied topically to the premalignant lesion.
The maximum tolerated energy density will be called the Maximum Tolerated Dose (MTD). Procedure: Fluorescence Diagnosis Imaging Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 6, 7 and 8 J/cm2.
干预措施: Fluorescence Diagnosis Imaging (Procedure)
Phase 2 - Treatment efficacy of PDT
Procedure: Fluorescence Diagnosis Imaging
Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 8 J/cm2.
干预措施: PDL-585, ScleroPLUS laser (Device)
Phase 2 - Treatment efficacy of PDT
Procedure: Fluorescence Diagnosis Imaging
Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 8 J/cm2.
干预措施: 5-Aminolevulinic Acid (Levulan KerastickTM) (Drug)
Phase 2 - Treatment efficacy of PDT
Procedure: Fluorescence Diagnosis Imaging
Interventions: Application of 5-ALA to lesion followed by activation with high power 585 nm pulsed dye laser (PDL-585, ScleroPLUS laser) at 8 J/cm2.
干预措施: Fluorescence Diagnosis Imaging (Procedure)
结局指标
主要结局
The Objective Response Rate is the Number of Participants With Significant Response (SR), Partial Response (PR) or No Response (NR).
时间窗: Day 90
The response rate was quantified by examination by an experienced head and neck surgeon and classified as follows: significant response (SR) was one where the lesion had greater than 75% resolution, partial response (PR) was one in which the lesion was reduced in size by at least 25%, and no response (NR) was one where the lesion was reduced by less than 25% in size.
Maximum Tolerated Dose
时间窗: Day 2
The traditional 3+3 dose escalation design was employed. Three cohorts were enrolled at 3 subjects per cohort, and treated with escalating radiant exposures of 6, 7, or 8 J/cm2. In each cohort, the number of dose-limiting toxicities (DLTs) were observed. Dose escalation rules were the same as those provided by Storer 1989.
次要结局
未报告次要终点