Safety Study Using Photodynamic Therapy Light Therapy for Patients With Chest Wall Progression of Breast Cancer and Satellite Metastases of Melanoma

The goal of this research is to conduct a Phase I clinical study to assess the toxicity,
safety and feasibility of a novel cancer treatment, Continuous Low Irradiance Photodynamic
Therapy (CLIPT). This research will provide translation of recent promising preclinical work
to human subjects with recurrent breast cancer.

BACKGROUND: Patients who develop post-mastectomy chest wall skin recurrence and fail
conventional radiation therapy have few therapeutic options that can result in durable
control. High-irradiance photodynamic therapy (PDT) has shown efficacy in patients with
chest-wall progression of breast cancer that have failed radiation, surgery, and
chemotherapy. However its clinical application has been severely limited as currently
employed methods of PDT result in virtually 100% of patients develop skin necrosis, large
areas of full-thickness ulceration, slow healing and chronic wound pain. In the rat and
rabbit-brain tumor models, reducing the laser irradiance and increasing the exposure time to
achieve a similar total fluence (fluence = irradiance x time) to standard PDT, avoids tissue
necrosis while inducing apoptosis in the tumor but not normal tissue.

HYPOTHESIS: Low dose-rate (low irradiance) PDT may reduce or eliminate skin toxicity and
enables treatment of skin/subcutaneous chest wall metastases in skin previously subjected to
ionizing radiation.

SPECIFIC AIMS:

1) determine the fluence of CLIPT resulting in toxicity (maximum tolerated dose), defined as
ulceration or necrosis of previously irradiated skin (non-tumor bearing skin within the
prior ionizing radiation field) or normal skin, 2) evaluate the feasibility, ergonomics and
safety of performing CLIPT via a proprietary electronically targetable fiber-optic "patch"
placed directly on tumor-bearing, surrounding uninvolved previously irradiated skin and
normal integument 3) study the tumor-bearing integument for clinical response to therapy by
measuring complete, partial and no response to CLIPT.

STUDY DESIGN: We will perform a standard dose (laser fluence) escalation trial (holding drug
level constant) in human subjects with post-mastectomy skin recurrences that have failed
ionizing radiation therapy and assess toxicity in previously irradiated and normal
integument.

POTENTIAL OUTCOMES & BENEFITS: Therapeutic options for post-mastectomy cutaneous recurrences
failing conventional radiotherapy are limited. If the pre-clinical results are replicated in
human subjects, Phase II studies to evaluate CLIPT would be warranted. The long-term goal is
to develop an unobtrusive, large-area CLIPT system in the form of a fiber-optically woven
"garment" that can be worn by the patient outside the hospital setting for repeated and
extended periods without causing skin breakdown or pain.