Project 1-lntraperitoneal PDT PI: Douglas Fraker Peritoneal carcinomatosis is a clinical problem which causes considerable morbidity and is uniformly fatal. Complete surgical resection is not possible, conventional radiation therapy is unable to safely treat all areas at risk, and systemic therapy with available agents is limited by drug delivery and efficacy. Intraperitoneal spread represents cancer progression on a complex surface and all areas of the abdominal cavity are at risk. During the first grant funding cycle we have demonstrated that surgical tumor debulking to minimal disease and intra-operative photodynamic therapy can be performed to treat all surfaces at risk. There were clinical responses seen in this heavily pre-treated population but the majority of patients recurred within the peritoneal cavity. This initial Phase II trial using photofrin was limited primarily by low photosensitizer retention in tumor compared to normal tissues. Other potential problems include the difficulty in delivering uniform light dose to a complex surface, and tumor hypoxia which may decrease PDT cytotoxicity. In the current proposal, Project I will address these problems by utilizing a second generation photosensitizer in combination with targeting agents to alter the signal transduction cascade in tumors. We propose to evaluate the second generation photosensitizer, benzoporphyrin derivative (BPD) in combination with the EGFR inhibitor, C225 based upon preliminary data suggesting this will increase the therapeutic index of IP PDT. Initial preclinical studies will be conducted in rabbits including peritoneal PDT at increasing doses of photosensitizer with and without bowel anastomoses. A Phase l/ll clinical trial will be performed on patients with peritoneal carcinomatosis from ovarian or gastro-intestinal cancers who have no other treatment options. The initial phase of the trial will identify and optimal dose of BPD and light energy. A second phase of the protocol will add C225 to assess response rates. In all parts of the trial malignant and normal tissue will be analyzed for sensitizer concentration, molecular markers related to PDT response, and intraoperatively for optical properties.

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National Cancer Institute (NCI)
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Kim, Michele M; Ghogare, Ashwini A; Greer, Alexander et al. (2017) On the in vivo photochemical rate parameters for PDT reactive oxygen species modeling. Phys Med Biol 62:R1-R48
Friedberg, Joseph S; Simone 2nd, Charles B; Culligan, Melissa J et al. (2017) Extended Pleurectomy-Decortication-Based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years. Ann Thorac Surg 103:912-919
Penjweini, Rozhin; Kim, Michele M; Zhu, Timothy C (2017) Three-dimensional finite-element based deformable image registration for evaluation of pleural cavity irradiation during photodynamic therapy. Med Phys 44:3767-3775
Ahn, Peter H; Finlay, Jarod C; Gallagher-Colombo, Shannon M et al. (2017) Lesion Oxygenation Associates with Clinical Outcomes in Premalignant and Early Stage Head and Neck Tumors Treated on a Phase 1 Trial of Photodynamic Therapy. Photodiagnosis Photodyn Ther :
Yan, Lesan; Miller, Joann; Yuan, Min et al. (2017) Improved Photodynamic Therapy Efficacy of Protoporphyrin IX-Loaded Polymeric Micelles Using Erlotinib Pretreatment. Biomacromolecules 18:1836-1844
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Kennedy, Gregory Thomas; Newton, Andrew; Predina, Jarrod et al. (2017) Intraoperative near-infrared imaging of mesothelioma. Transl Lung Cancer Res 6:279-284
Zhu, Timothy C; Kim, Michele M; Ong, Yi-Hong et al. (2017) A summary of light dose distribution using an IR navigation system for Photofrin-mediated Pleural PDT. Proc SPIE Int Soc Opt Eng 10047:
Gemmell, Nathan R; McCarthy, Aongus; Kim, Michele M et al. (2017) A compact fiber-optic probe-based singlet oxygen luminescence detection system. J Biophotonics 10:320-326
Kim, Michele M; Penjweini, Rozhin; Zhu, Timothy C (2017) Evaluation of singlet oxygen explicit dosimetry for predicting treatment outcomes of benzoporphyrin derivative monoacid ring A-mediated photodynamic therapy. J Biomed Opt 22:28002

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