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Treatment of Oral Premalignant Lesions With 5-ALA PDT

Primary Purpose

Leukoplakia, Erythroplakia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PDL-585, ScleroPLUS laser
5-Aminolevulinic Acid (Levulan KerastickTM)
Fluorescence Diagnosis Imaging
Sponsored by
University of Arkansas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukoplakia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arkansas for Medical Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1 light dose escalation

Phase 2 - Treatment efficacy of PDT

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
December 5, 2007
Last Updated
March 4, 2015
Sponsor
University of Arkansas
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1. Study Identification

Unique Protocol Identification Number
NCT00571974
Brief Title
Treatment of Oral Premalignant Lesions With 5-ALA PDT
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arkansas

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukoplakia, Erythroplakia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 light dose escalation
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 - Treatment efficacy of PDT
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
PDL-585, ScleroPLUS laser
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
5-Aminolevulinic Acid (Levulan KerastickTM)
Other Intervention Name(s)
5-ALA
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Fluorescence Diagnosis Imaging
Intervention Description
FD Image taken prior to PDL-585 usage
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
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.
Time Frame
Day 2
Title
The Objective Response Rate is the Number of Participants With Significant Response (SR), Partial Response (PR) or No Response (NR).
Description
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.
Time Frame
Day 90

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gal Shafirstein, PhD
Organizational Affiliation
University of Arkansas
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22106236
Citation
Shafirstein G, Friedman A, Siegel E, Moreno M, Baumler W, Fan CY, Morehead K, Vural E, Stack BC Jr, Suen JY. Using 5-aminolevulinic acid and pulsed dye laser for photodynamic treatment of oral leukoplakia. Arch Otolaryngol Head Neck Surg. 2011 Nov;137(11):1117-23. doi: 10.1001/archoto.2011.178.
Results Reference
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Treatment of Oral Premalignant Lesions With 5-ALA PDT

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