Treatment of Oral Premalignant Lesions With 5-ALA PDT

Phase 1

Completed

Conditions: Erythroplakia
Leukoplakia

Interventions: Device: PDL-585, ScleroPLUS laser
Drug: 5-Aminolevulinic Acid (Levulan KerastickTM)
Procedure: Fluorescence Diagnosis Imaging

Registration Number: NCT00571974

Lead Sponsor: University of Arkansas

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Phase 1 light dose escalation	Fluorescence Diagnosis Imaging	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.
Phase 1 light dose escalation	PDL-585, ScleroPLUS laser	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.
Phase 1 light dose escalation	5-Aminolevulinic Acid (Levulan KerastickTM)	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.
Phase 2 - Treatment efficacy of PDT	5-Aminolevulinic Acid (Levulan KerastickTM)	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.
Phase 2 - Treatment efficacy of PDT	PDL-585, ScleroPLUS laser	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.
Phase 2 - Treatment efficacy of PDT	Fluorescence Diagnosis Imaging	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.

Primary Outcome Measures

Name	Time	Method
The Objective Response Rate is the Number of Participants With Significant Response (SR), Partial Response (PR) or No Response (NR).	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	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.

Secondary Outcome Measures