Photodynamic Therapy (PDT) for Benign Dermal Neurofibromas (NF1)
GENERAL OBJECTIVE The general objective is to assess the safety and efficacy of photodynamic therapy (PDT) in the treatment of neurofibromatosis 1 (NF1) tumors in the skin.
SPECIFIC OBJECTIVE This is a light dose escalation pilot study to determine the safety and efficacy of PDT using 5-aminolevulinic acid (ALA) and 630 nm light in the treatment of benign dermal neurofibromas.
Specifically, the primary goal of the current study is to determine the maximum tolerable light doses that can be administered to subjects undergoing topical photoillumination photodynamic therapy with standard application of Levulan Kerastick (ALA) for Topical Solution.
|Neurofibromatoses||Drug: Levulan (5-aminolevulinic acid) uptake. Drug: Levulan (5-aminolevulinic acid) photodynamic therapy.||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Photodynamic Therapy for Benign Dermal Neurofibromas Using Levulan Kerastick For Topical Solution, Plus Illumination With Red Light|
- Part 1: Photosensitizer uptake [ Time Frame: 24 hours ]Measurement of the ratio of the mean fluorescence intensity in excised, sectioned tumors, to the fluorescence in immediately adjacent tissue, as determined by fluorescence microscopy
- Part 2: Maximum tolerated dose (MTD) [ Time Frame: 48 hours ]Maximum tolerated dose (MTD) as determined by dose limiting toxicity.
- Part 1: Optimal Occlusion time [ Time Frame: 24 hours ]An optimal occlusion time may be apparent from the results of the three time points. If no optimal occlusion time is seen, any occlusion time from 3-24 hours may be chosen for part 2. This secondary outcome measure is not critical to continuing the study, but may be useful in guiding treatment protocols
- Part 2: Efficacy - lesion size [ Time Frame: 1 year ]Decrease in lesion size as measured by ruler (directly or using a digital photograph). The area of the lesion will be estimated by the nurse or dermatologist by measuring the radius if circular, or by length and width if not. Irregular areas can be measured using the application of digital imaging programs such as ImageJ to the digital photograph.
- Part 2: Cosmetic Improvement [ Time Frame: 1 year ]Potential cosmetic improvement using subject satisfaction scale.
- Part 2: Pain Reduction [ Time Frame: 1 year ]Potential pain reduction, as measured by standard visual analog 1-10 scale.
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||November 2017|
|Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Experimental: Part 1
Levulan (5-aminolevulinic acid) uptake.
Drug: Levulan (5-aminolevulinic acid) uptake.
8 adult subjects will be needed, two subjects for each incubation time point, and one each for negative and positive controls. Multiple lesions for each subject may be treated in order to provide better estimations of fluorescence levels.
Tumors will be incubated with Levulan under occlusion for 3, 6, or 24 hrs. A minimum of three tumors per group on the same subject will be incubated with Levulan or vehicle only for three hours. Tumors will then be excised in the normal manner. A minimum of three untreated control tumors will be excised. Thus there will be three groups of tumors excised per subject. Tumors will be sectioned vertically and checked for PpIX using fluorescence microscopy. Negative controls will now consist of untreated tumors and tumors incubated with vehicle only for 3 hours on the same subjects as the Levulan treated tumors. Positive controls will consist of intralesional injection of saline-dissolved ALA approximately one hour before excision.
Experimental: Part 2
Levulan (5-aminolevulinic acid) photodynamic therapy.
Drug: Levulan (5-aminolevulinic acid) photodynamic therapy.
2-18 adult subjects with 3-8 lesions per (Levulan or control) group per subject. Controls will consist of lesions treated with vehicle only and light illumination, and will be paired with treatment lesions by the study doctor. Control lesions will be treated on the same subject as study lesions. Levulan will be incubated for 3-24 hours under occlusion, then gently rinsed with water and patted dry. Photoactivation of lesions treated with Levulan is then accomplished with 630 nm red light illumination. 630 nm light will be applied for varying periods of time in order to achieve a dose of 25, 50, or 100 J/cm2. There will be one treatment session per subject. Treatments will include a minimum of three test lesions and an additional three control lesions.
STUDY DESIGN This protocol is a Phase I light dose escalation pilot study to determine the safety and, secondarily, the efficacy of PDT using Levulan and 630 nm light in the treatment of benign dermal neurofibromas. This protocol represents the first two parts of a planned three part study including both pediatric and adult subjects. Part 1 will consist of studying the penetration and uptake of the PS in neurofibromas that are scheduled for excision. These tumors will be excised for therapeutic reasons unrelated to this study, and so this study will place no further burden on the subject other than a 3-24 hr incubation of the Levulan on the tumor prior to excision. The primary hypothesis to be tested is whether Levulan will accumulate, and be converted to PpIX, by the tumor tissue more than by the surrounding normal tissue. Secondary hypotheses are that tumors incubated with Levulan will show greater fluorescence than untreated tumors and tumors incubated with vehicle only (placebo application).
As the Institutional Review Boards involved generally desire pilot data on adult populations first, we will with then proceed with the adult clinical trial portion of this protocol as part 2. Part 2 will use the optimum incubation time, if one has been identified in part 1, and add a dose escalation study of the amount of red light used to activate the Levulan. Part 3, with pediatric subjects, will commence at a future date, pending review of the initial adult study results.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682811
|United States, Wisconsin|
|The Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Harry T Whelan, MD||Medical College of Wisconsin|