Treatment of Oral Premalignant Lesions With 5-ALA PDT

NCT00571974 | Completed Phase 1 Results

• 1 other identifier: 51439
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukoplakia; Erythroplakia

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

Phase 1 light dose escalation

EXPERIMENTAL

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; Drug: 5-Aminolevulinic Acid (Levulan KerastickTM); Procedure: Fluorescence Diagnosis Imaging

Phase 2 - Treatment efficacy of PDT

EXPERIMENTAL

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; Drug: 5-Aminolevulinic Acid (Levulan KerastickTM); Procedure: Fluorescence Diagnosis Imaging

Interventions

PDL-585, ScleroPLUS laser DEVICE

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

Phase 1 light dose escalation; Phase 2 - Treatment efficacy of PDT

5-Aminolevulinic Acid (Levulan KerastickTM) DRUG

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

Also known as: 5-ALA

Phase 1 light dose escalation; Phase 2 - Treatment efficacy of PDT

Fluorescence Diagnosis Imaging PROCEDURE

FD Image taken prior to PDL-585 usage

Phase 1 light dose escalation; Phase 2 - Treatment efficacy of PDT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (1)

• 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.

  PMID: 22106236 RESULT

MeSH Terms

Conditions

Leukoplakia; Erythroplasia

Interventions

Aminolevulinic Acid

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Since all but one subject responded to treatment, no correlative analysis of response with change in expression of p53 or Ki-67 was undertaken.

Results Point of Contact

• Title: Gal Shafirstein, D.Sc.
• Organization: Roswell Park Cancer Institute

Gal.Shafirstein@RoswellPark.org

716-845-4025

Study Officials

• Gal Shafirstein, PhD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2007
• First Posted: December 12, 2007
• Study Start: January 1, 2007
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: March 24, 2015
• Results First Posted: November 13, 2012

Record last verified: 2015-03

Locations

US (1)