A Phase I Trial of Continuous Low-Irradiance Photodynamic Therapy (CLIPT) for Patients Failing Radiation Therapy
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
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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose Limiting Toxicity (full thickness ulceration and/or necrosis of the skin)
48 hours to 7 days after treatment
Roger Graham, MD
Tufts Medical Center, Department of Surgery
United States: Federal Government
Komen Award ID# -BCTR0707871
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