Phase I Photodynamic Therapy (PDT) for Benign Dermal Neurofibromas (NF1)
Condition: Neurofibromatoses
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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.
    

Intervention name(s): 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 type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment