Treatment of Oral Premalignant Lesions With 5-ALA PDT

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Leukoplakia, Erythroplakia

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 light dose escalation<br>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. | Device: PDL-585, ScleroPLUS laser<br>* PDT Treatment; emits light with 585 nm wavelength in pulses of 1.5 milliseconds in sections of 5 mm diameter to target the lesion and surrounding tissue<br>Drug: 5-Aminolevulinic Acid (Levulan KerastickTM)<br>* Topically administered; incubation time 60-180 minutes; single dose (345 mg of active 5-ALA in 1.5 ml solution); soaked onto white gauze and applied to lesion, covered with sterile Xeroform gauze<br>* Other names: 5-ALA;Procedure: Fluorescence Diagnosis Imaging<br>* FD Image taken prior to PDL-585 usage<br>|
| Experimental: Phase 2 - Treatment efficacy of PDT<br>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. | Device: PDL-585, ScleroPLUS laser<br>* PDT Treatment; emits light with 585 nm wavelength in pulses of 1.5 milliseconds in sections of 5 mm diameter to target the lesion and surrounding tissue<br>Drug: 5-Aminolevulinic Acid (Levulan KerastickTM)<br>* Topically administered; incubation time 60-180 minutes; single dose (345 mg of active 5-ALA in 1.5 ml solution); soaked onto white gauze and applied to lesion, covered with sterile Xeroform gauze<br>* Other names: 5-ALA;Procedure: Fluorescence Diagnosis Imaging<br>* FD Image taken prior to PDL-585 usage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | 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. | Day 2 | 
| The Objective Response Rate is the Number of Participants With Significant Response (SR), Partial Response (PR) or No Response (NR). | 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. | Day 90 |