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Treatment of Oral Premalignant Lesions With 5-ALA PDT

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ClinicalTrials.gov Identifier: NCT00571974
Recruitment Status : Completed
First Posted : December 12, 2007
Results First Posted : November 13, 2012
Last Update Posted : March 24, 2015
Sponsor:
Information provided by (Responsible Party):
University of Arkansas

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Leukoplakia
Erythroplakia
Interventions Device: PDL-585, ScleroPLUS laser
Drug: 5-Aminolevulinic Acid (Levulan KerastickTM)
Procedure: Fluorescence Diagnosis Imaging
Enrollment 29

Recruitment Details Subjects were identified in the head and neck oncology clinic and enrolled into the study within the time period of January 1, 2007 to November 18, 2009.
Pre-assignment Details Screen failure did meet incl./excl. criteria
Arm/Group Title Phase I Phase II
Hide Arm/Group Description

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).

During Phase II, to assess the treatment efficacy of PDL-585 when used at the MTD in combination with 5-ALA applied topically to the premalignant lesion. Treatment efficacy will be assessed by means of the 90-day Objective Response rate observed among study subjects treated at the MTD.
Period Title: Phase I
Started 9 0
Completed 9 0
Not Completed 0 0
Period Title: Phase II
Started 0 21 [1]
Completed 0 17
Not Completed 0 4
[1]
3 participants are from phase I
Arm/Group Title Phase I Phase II Total
Hide Arm/Group Description

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).

During Phase II, to assess the treatment efficacy of PDL-585 when used at the MTD in combination with 5-ALA applied topically to the premalignant lesion. Treatment efficacy will be assessed by means of the 90-day Objective Response rate observed among study subjects treated at the MTD. Total of all reporting groups
Overall Number of Baseline Participants 11 18 29
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 11 participants 18 participants 29 participants
<=18 years 0 0 0
Between 18 and 80 years 11 18 29
>=80 years 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 18 participants 29 participants
Female
7
  63.6%
7
  38.9%
14
  48.3%
Male
4
  36.4%
11
  61.1%
15
  51.7%
1.Primary Outcome
Title Maximum Tolerated Dose
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Three cohorts were enrolled at 3 subjects per cohort, and treated with escalating radiant exposures (laser doses) of 6, 7, or 8 J/cm2. In each cohort, the number of dose-limiting toxicities (DLTs) were observed. The highest radiant light dose attained that did not produce more than 2 DLTs was declared to be the maximum tolerated dose (MTD).
Arm/Group Title Phase I
Hide Arm/Group Description:
Participants in the Phase I part of the study.
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: J/cm2
8
2.Primary Outcome
Title The Objective Response Rate is the Number of Participants With Significant Response (SR), Partial Response (PR) or No Response (NR).
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Simon two-stage minimax design with 9 subjects in the first stage and 8 subjects in the second stage, yielding 17 subjects overall.
Arm/Group Title Phase II
Hide Arm/Group Description:
Subjects treated with the MTD.
Overall Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: participants
Participants with Significant Response (SR) 7
Participants with Partial Response (PR) 9
Participants with no Response (NR) 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase II
Comments The Simon two-stage minimax design with 9 subjects in the first stage and 8 subjects in the second stage, yielding 17 subjects overall. This design’s early termination rule was ≤3/9 responses in the first stage, and its success criterion was ≥7/17 responses overall. This design had 80% power at 5% alpha to distinguish an efficacious 50% response rate from a null-hypothesis 20% response rate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments One-sided exact binomial test to compare the observed response rate to the 20% rate envisioned under the original null hypothesis.
Method One-sided exact binomial test
Comments Because all but one subject responded to treatment, the Fisher’s exact test was addedd.
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I Phase II
Hide Arm/Group Description

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).

During Phase II, to assess the treatment efficacy of PDL-585 when used at the MTD in combination with 5-ALA applied topically to the premalignant lesion. Treatment efficacy will be assessed by means of the 90-day Objective Response rate observed among study subjects treated at the MTD.
All-Cause Mortality
Phase I Phase II
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Phase I Phase II
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/9 (0.00%)      0/21 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase I Phase II
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/9 (100.00%)      2/21 (9.52%)    
General disorders     
Dry mouth *  1/9 (11.11%)  1 0/21 (0.00%)  0
Bad breath *  1/9 (11.11%)  1 0/21 (0.00%)  0
Insomnia   1/9 (11.11%)  1 0/21 (0.00%)  0
Swollen lip *  1/9 (11.11%)  1 0/21 (0.00%)  0
Redness on chin *  1/9 (11.11%)  1 0/21 (0.00%)  0
Taste altered *  1/9 (11.11%)  1 0/21 (0.00%)  0
Burning sensation *  1/9 (11.11%)  1 0/21 (0.00%)  0
Sensitive to cold   1/9 (11.11%)  1 0/21 (0.00%)  0
Sensitive   1/9 (11.11%)  1 0/21 (0.00%) 
Raw   1/9 (11.11%)  1 0/21 (0.00%) 
Soreness *  1/9 (11.11%)  1 0/21 (0.00%) 
Swelling *  1/9 (11.11%)  1 0/21 (0.00%) 
Nervous system disorders     
Pain   2/9 (22.22%)  2 2/21 (9.52%)  2
Psychiatric disorders     
Depression   1/9 (11.11%)  1 0/21 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Since all but one subject responded to treatment, no correlative analysis of response with change in expression of p53 or Ki-67 was undertaken.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Gal Shafirstein, D.Sc.
Organization: Roswell Park Cancer Institute
Phone: 716-845-4025
Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT00571974     History of Changes
Other Study ID Numbers: 51439
First Submitted: December 5, 2007
First Posted: December 12, 2007
Results First Submitted: May 11, 2012
Results First Posted: November 13, 2012
Last Update Posted: March 24, 2015