Phase I Photodynamic Therapy (PDT) for Benign Dermal Neurofibromas (NF1)

Photodynamic Therapy for Benign Dermal Neurofibromas Using Levulan Kerastick For Topical Solution, Plus Illumination With Red Light

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 633 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.

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 633 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.

Inclusion Criteria:

Subjects with NF1 will be selected for photodynamic therapy on the following criteria.

1. Age: 18 years or older.
2. NF1 will be diagnosed by American Academy of Neurology guidelines.
3. Location of tumor: cutaneous, trunk or limbs only.
4. Tumor type: superficial dermal neurofibromas, less than or equal to 4 mm deep.
5. Growth confirmation: direct measurement for the dermal neurofibromas, ruler and photo-volumetric method.
6. Informed consent of subject.
7. Absence of any other malignancy.
8. Only failures to meet criteria 1-6 due to the primary disease will be disqualifying

Exclusion Criteria:

Subjects will be excluded from participation in the study on the basis of the following:

1. Life expectancy less than 1 year.
2. Pregnancy.
3. Inability to consent.
4. Cutaneous photosensitivity to the wavelengths used to activate PDT.
5. A diagnosis of porphyria.
6. Allergy to aminolevulinic acid or any of the Topical Solution Vehicle components.
7. Previous chemotherapy within 6 weeks of proposed PDT.
8. Other concurrent tumor therapy. -