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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Medical College of Wisconsin
Sponsor:
Information provided by (Responsible Party):
Harry T Whelan, MD, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01682811
First received: September 5, 2012
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Neurofibromatoses
Drug: Levulan (5-aminolevulinic acid) uptake.
Drug: Levulan (5-aminolevulinic acid) photodynamic therapy.
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Photodynamic Therapy for Benign Dermal Neurofibromas Using Levulan Kerastick For Topical Solution, Plus Illumination With Red Light

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Part 1: Photosensitizer uptake [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) as determined by dose limiting toxicity.


Secondary Outcome Measures:
  • Part 1: Optimal Occlusion time [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Potential cosmetic improvement using subject satisfaction scale.

  • Part 2: Pain Reduction [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Potential pain reduction, as measured by standard visual analog 1-10 scale.


Estimated Enrollment: 30
Study Start Date: November 2011
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01682811

Contacts
Contact: Debbie Dye 414-266-7544 ddye@mcw.edu

Locations
United States, Wisconsin
The Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Harry T Whelan, MD    414-266-7544    hwhelan@mcw.edu   
Sponsors and Collaborators
Harry T Whelan, MD
Investigators
Principal Investigator: Harry T Whelan, MD Medical College of Wisconsin
  More Information

No publications provided

Responsible Party: Harry T Whelan, MD, Bleser Professor of Neurology, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01682811     History of Changes
Other Study ID Numbers: PRO 14555
Study First Received: September 5, 2012
Last Updated: February 25, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neurofibroma
Neurofibromatoses
Neurofibromatosis 1
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Aminolevulinic Acid
Photosensitizing Agents
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 11, 2014