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

Harry T Whelan, MD

Status and phase: Completed; Phase 1

Conditions: Neurofibromatoses

Treatments: Drug: Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 2; Drug: Part 1 Levulan injection; Drug: Part 1 Levulan surface application; Drug: Part 1 Levulan surface application twice; Drug: Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 3; Drug: Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 1; Drug: Part 1 Levulan surface application twice with microneedling

Study type: Interventional

Funder types: Other

Identifiers

NCT01682811

PRO 14555

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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. -

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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20 participants in 7 patient groups

Part 1 Levulan injection

Experimental group

Description:

5-aminolevulinic acid uptake by control lesions after Levulan vehicle (placebo) injection and 3 hr incubation, and by Levulan treated lesions after 3 or 24 hr incubation.

Treatment:

Drug: Part 1 Levulan injection

Part 1 Levulan painting

Experimental group

Description:

5-aminolevulinic acid uptake by control lesions after Levulan vehicle (placebo) surface application and 3 hr incubation, and by Levulan treated lesions and 3 or 24 hr incubation.

Treatment:

Drug: Part 1 Levulan surface application

Part 1 Levulan painted twice

Experimental group

Description:

5-aminolevulinic acid uptake by control lesions after Levulan vehicle (placebo) surface application twice or by Levulan treated lesions twice and 24 hr incubation.

Treatment:

Drug: Part 1 Levulan surface application twice

Part 1 Levulan painted twice with microneedling

Experimental group

Description:

5-aminolevulinic acid uptake by control lesions after Levulan vehicle (placebo) surface application twice or by Levulan treated lesions twice and 24 hr incubation. All lesions prepared with microneedling.

Treatment:

Drug: Part 1 Levulan surface application twice with microneedling

Part 2 Dose level 1 50 J/cm^2

Experimental group

Description:

Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 1 - 50 J/cm\^2 633 nm red light to Levulan vehicle (placebo) treated control lesions or Levulan treated lesions and 24 hr incubation. Follow-ups on day 2 for punch biopsies, 14-28 days for evaluation of cutaneous adverse events, and every 3 months up to one year for lesion measurements.

Treatment:

Drug: Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 1

Part 2 Dose level 2 100 J/cm^2

Experimental group

Description:

Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 2 - 100 J/cm\^2 633 nm red light to Levulan vehicle (placebo) treated control lesions or Levulan treated lesions and 24 hr incubation. Follow-ups on day 2 for punch biopsies, 14-28 days for evaluation of cutaneous adverse events, and every 3 months up to one year for lesion measurements.

Treatment:

Drug: Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 2

Part 2 Dose level 3 200 J/cm^2

Experimental group

Description:

Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 3 - 200 J/cm\^2 633 nm red light to Levulan vehicle (placebo) treated control lesions or Levulan treated lesions and 24 hr incubation. Follow-ups on day 2 for punch biopsies, 14-28 days for evaluation of cutaneous adverse events, and every 3 months up to one year for lesion measurements.

Treatment:

Drug: Levulan (5-aminolevulinic acid) photodynamic therapy - Dose level 3