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Interstitial Chemophototherapy with Light-Activated Nanoparticulate Doxorubicin

光激活纳米颗粒阿霉素间质化学光疗

基本信息

批准号：
10384796
负责人：
GAL SHAFIRSTEIN
金额：
$ 100.14万
依托单位：
POP BIOTECHNOLOGIES, INC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-06 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10384796
关键词：
Address Animals Benchmarking Biotechnology Buffaloes Cancerous Canis familiaris Characteristics Chronic viral hepatitis Clinic Clinical Clinical Research Computer Models Data Dose Doxorubicin Elements Encapsulated Experimental Animal Model Formulation Future Goals Hepatitis B Human In complete remission Lasers Licensing Light Lighting Lipids Liposomes Liver neoplasms Locally Advanced Malignant Neoplasm Magnetic Resonance Imaging Malignant neoplasm of liver Maximum Tolerated Dose Measures Methods Modeling Monitor Mus Nature Oryctolagus cuniculus PUVA Photochemotherapy Patients Persons Pharmaceutical Preparations Phase Phospholipids Phototherapy Pilot Projects Porphyrins Primary Neoplasm Primary carcinoma of the liver cells Rattus Reporting Rodent Route Safety Serum Small Business Technology Transfer Research Surface Survival Rate Testing Therapeutic Tissues Toxic effect Toxicology Translating Vaccines Vascular Permeabilities Woodchuck Work absorption base blood perfusion contrast enhanced dosimetry first-in-human interstitial light dosimetry liver cancer patient meetings nanoparticulate novel novel therapeutics primary endpoint response secondary endpoint success treatment planning tumor tumor ablation

项目摘要

Summary Our goal is to commercialize interstitial chemo-phototherapy (I-CPT) as a new therapeutic option for locally advanced liver cancers. Doxorubicin (Dox) can be actively loaded into long circulating, serum-stable, porphyrin- phospholipid (PoP) liposomes and be released with 665-nm laser light (PhotoDox). This approach leads to vastly enhanced drug accumulation in irradiated tissues, resulting in ultrapotent tumor ablation. In the phase I STTR, we employed this dosimetry-treatment planning platform to guide light administration of I-CPT with PhotoDox. We demonstrated that this treatment planning with light dosimetry is effective in ablating large orthotopic hepatocellular carcinoma tumors in rats. In this phase II STTR application we propose to further advance I-CPT with PhotoDox towards an IND for enabling future clinical studies. To that end we propose to complete the following aims: Aim 1: Optimizing I-CPT with PhotoDox for a durable complete response of large spontaneous hepatocellular carcinoma in a woodchuck model. The woodchuck model is the largest experimental animal model with spontaneous locally advanced hepatocellular carcinoma (HCC) in the context of chronic viral hepatitis and liver cancer, as seen in people with hepatitis B. In pilot studies, we have safely dosed PhotoDox to woodchucks, confirmed the characteristic long-circulating nature of PhotoDox and applied the FEM based treatment planning and dosimetry to safely treat HCC (~50 cm3) with I-CPT in woodchucks. We will address the key question: What are the optimal light settings for I-CPT with PhotoDox in the treatment of large HCC? Aim 2: Generate IND- enabling data on the toxicity of I-CPT with PhotoDox. POP BIO has previously generated non-GLP toxicity data of PhotoDox in rats including cursory establishment of the maximum tolerated dose. Since then, POP BIO has held a pre-IND meeting with the FDA, who confirmed the suitability of the 505(b)(2) route for components of PhotoDox and provided guidance about the required toxicological studies required prior to first-in-human studies. We will address the key question: What is the toxicity of PhotoDox under GLP studies? This translational Phase II project will provide required data for an IND submission to the FDA by providing valuable relevant to understanding I-CPT treatment in the context of human liver cancer patients. If successful, I-CPT with PhotoDox stands to benefit the majority of new liver cancer patients, who have inoperable and problematic primary tumors.

总结