safety study using photodynamic therapy light therapy for patients with chest wall progression of breast cancer and satellite metastases of melanoma

Conditions: Breast Cancer; Skin Cancer

Summary: this research is intended to explore a new approach to therapy when breast cancer recurs in the skin. the treatment, known as continuous low-irradiance photodynamic therapy, or clipt, has shown great promise in animal studies. the investigators goal is to evaluate clipt in people, using a novel light delivery system, to assess its side effects and the benefit it has in treating cancer. the investigators goal is to develop a safe, effective therapy that can be given in the doctor's office or possibly at home.

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.

Eligibility criteria:
inclusion criteria: * patients \> 18 years of age, with primary or metastatic cutaneous tumors that have been previously irradiated. * patients must have a target lesion and normal peri-umbilical skin that can be covered by the fiber-optic mesh used to deliver clipt (10 x 10 cm for target lesion, and 1 x 1 cm for control site). * patients must have a target lesion in a location other than the hands, feet, genitals, or face. lesions in those locations will be excluded. * patients must sign informed consent. exclusion criteria: * patients must not have received any systemic anti-cancer therapy within 30 days prior to enrolling in this study. * patients must not have received radiation therapy to the target site within 60 days of enrolling on this study. * patients with medical conditions associated with photosensitivity, such as cutaneous porphyria or a collagen vascular disease, or with known allergies to porphyrins will be excluded. * pregnant and nursing patients will be excluded. women of child-bearing potential must have a negative serum or urine pregnancy test prior to enrollment. * patients taking medications known to cause photosensitivity (tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, and fluoroquinolones) will be excluded. * laboratory values (note: these are provided by the potential patient): * absolute neutrophil count \> 1000. * patients with severe hepatic dysfunction (total bilirubin, ast, or alt \> five times upper limit of normal) will be excluded. * adequate coagulation status as indicated by platelet count \> 50,000, pt and ptt \< 1.5 time the upper limit of normal. * negative urine or serum pregnancy test note: no cost to patient, and no compensation provided.

Keywords: cancer skin metastases chest wall progression of breast cancer malignant melanoma photodynamic therapy photophrin satellite and in-transit metastases of malignant melanoma skin cancer