Phase I Photodynamic Therapy (PDT) for Benign Dermal Neurofibromas (NF1)
Condition: Neurofibromatoses
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
Intervention: Part 1 Levulan injection; Part 1 Levulan surface application; Part 1 Levulan surface application twice; Part 1 Levulan surface application twice with microneedling; Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 1; Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 2; Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 3
Intervention description: Control or treatment lesions will be injected with Levulan vehicle only or active drug and incubated under occlusion for 3 or 24 hrs. A minimum of three lesions per group on the same subject will be treated. Lesions will then be excised in the normal manner, sectioned vertically, and checked for Protoporphyrin IX using fluorescence microscopy.; Control or treatment lesions will be painted with Levulan vehicle only or active drug, allowed to dry, and incubated under occlusion for 3 or 24 hrs. A minimum of three lesions per group on the same subject will be treated. Lesions will then be excised in the normal manner, sectioned vertically, and checked for Protoporphyrin IX using fluorescence microscopy.; Control or treatment lesions will be painted twice with Levulan vehicle only or active drug, allowed to dry between and after applications, and incubated under occlusion for 3 hrs. A minimum of three tumors per group on the same subject will be treated. Lesions will then be excised in the normal manner, sectioned vertically, and checked for Protoporphyrin IX using fluorescence microscopy.; Control or treatment lesions will be prepared with microneedling, painted twice with Levulan vehicle only or active drug, allowed to dry between and after applications, and incubated under occlusion for 24 hrs. A minimum of three tumors per group on the same subject will be treated. Lesions will then be excised in the normal manner, sectioned vertically, and checked for Protoporphyrin IX using fluorescence microscopy.; 2-6 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 633 nm red light illumination. 633 nm light will be applied for 8 minutes to achieve a dose of 50 J/cm^2. There will be one treatment session per subject. Treatments will include a minimum of three test lesions and an additional three control lesions.; 2-6 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 633 nm red light illumination. 633 nm light will be applied for 16 minutes to achieve a dose of 100 J/cm^2. There will be one treatment session per subject. Treatments will include a minimum of three test lesions and an additional three control lesions.; 2-6 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 633 nm red light illumination. 633 nm light will be applied for 32 minutes to achieve a dose of 200 J/cm^2. There will be one treatment session per subject. Treatments will include a minimum of three test lesions and an additional three control lesions.
Intervention MeSH terms: Aminolevulinic Acid
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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. -