The overall goal of this project is to determine the clinical and cellular/molecular effects of PDT using Pc 4 on stage 1A-2A CTCL/MF. CTCL is a rare cutaneous malignancy with a prevalence of less than 200,000. It is hypothesized that topically applied Pc 4 followed by red light is a saf and tolerable treatment for early stage CTCL/MF.
The aim i s to demonstrate both clinical safety and tissue biological effects using skin biopsies of Pc 4-PDT treated versus untreated control lesions. These biopsies will be analyzed at the gene and protein expression level to determine potential biomarkers of response to PDT in CTCL, that can be used to optimize future protocols for Phase 2 and 3 clinical trials. The known photostability of Pc 4 will be utilized by evaluating the benefits of repeated photoexposures. This will be aided by an in vivo imaging device that measures Pc 4 levels in real time in skin lesions through fluorescence spectroscopy.

Public Health Relevance

Cutaneous T-cell lymphoma (CTCL) of the Mycosis Fungoides (MF) variant is a rare but serious skin malignancy. Unlike other skin cancers such as epithelial carcinomas that can be surgically removed, CTCL is a chronic recalcitrant condition that appears initially as eczema-like patches and plaques, prior to progression into tumors or even a leukemic stage with significant morbidity and a 3-year median survival. The presentation of CTCL is such that it is not amenable to surgical removal. It also involves an unclear etiology and a complex pathogenesis, which makes the management of this disease even more difficult. In fact, only a select number of dermatologists are comfortable and well-versed in managing CTCL/MF. Current treatment options are not consistently effective. Some of the approved drugs are also very expensive (e.g. topical and systemic retinoids, dinileukin diftitox or Ontak(R), vorinostat or Zolinza(R)) and have the potential for numerous side effects (e.g. immunosuppression, risk for other malignancies, cardiotoxicity, etc). Hence, there is clearly a need to develop therapies for CTCL that are safe, effective, and affordable. This study aims to address that need by initiating a Phase I controlled clinical trial on silicon phthalocyanine Pc 4 for photodynamic therapy (PDT) of early stage CTCL (IA-IIA). This modality involves a simple topical application of the photosensitizer Pc 4, followed by photoexposure to 675 nm red light. Pc 4-PDT has already been shown safe and tolerable in an initial study of 43 patients with various skin neoplasms. It has also been found safe and tolerable in an ongoing Phase 1 clinical trial for psoriasis in which 17 subjects have been treated to date. A clinical trial focused on CTCL/MF, with mechanistic studies, will enhance the development of this therapy, and will pave the way for new strategies in the management of this rare but debilitating disease.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project (R01)
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Special Emphasis Panel (ZFD1-OPD-N (S1))
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Case Western Reserve University
Schools of Medicine
United States
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