Treatment of Oral Premalignant Lesions With 5-ALA PDT

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00571974
First received: December 5, 2007
Last updated: November 6, 2012
Last verified: November 2012

December 5, 2007
November 6, 2012
January 2007
January 2012   (final data collection date for primary outcome measure)
  • Maximum Tolerated Dose [ Time Frame: Day 2 ] [ Designated as safety issue: Yes ]
    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). [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
    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 [ Time Frame: duration of study ] [ Designated as safety issue: Yes ]
  • Objective Response Rate [ Time Frame: Day 90 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00571974 on ClinicalTrials.gov Archive Site
Not Provided
Biomarkers [ Time Frame: at biopsies before and after treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Treatment of Oral Premalignant Lesions With 5-ALA PDT
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.

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukoplakia
  • Erythroplakia
  • Device: PDL-585, ScleroPLUS laser
    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
  • Drug: 5-Aminolevulinic Acid (Levulan KerastickTM)
    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
    Other Name: 5-ALA
  • Procedure: Fluorescence Diagnosis Imaging
    FD Image taken prior to PDL-585 usage
  • Experimental: 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.

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

    Interventions:
    • Device: PDL-585, ScleroPLUS laser
    • Drug: 5-Aminolevulinic Acid (Levulan KerastickTM)
    • Procedure: Fluorescence Diagnosis Imaging
Shafirstein G, Friedman A, Siegel E, Moreno M, Bäumler 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
29
January 2012
January 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00571974
51439
No
University of Arkansas
University of Arkansas
Not Provided
Principal Investigator: Gal Shafirstein, PhD University of Arkansas
University of Arkansas
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP