Ultrasound-based diagnostic and monitoring of bladder cancer treatment with drug released from nanoparticles

基于超声的诊断和监测纳米颗粒释放药物治疗膀胱癌

基本信息

批准号：
10356881
负责人：
Joe Assouline
金额：
$ 95.69万
依托单位：
NANOMEDTRIX, LLC
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-07 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10356881
关键词：
Address Adult Adverse event Adverse reactions Alpha Particles Animal Model Animal Testing Animals BCG Live Bacillus Calmette-Guerin Therapy Bladder Bladder Neoplasm Cancer Patient Canis familiaris Carcinoma Carcinoma in Situ Cells Chemistry Clinical Clinical Trials Contracts Cultured Cells Cyclic GMP Data Data Set Development Diagnostic Disease Dose Drug Formulations Drug Industry Drug Kinetics Ensure Epirubicin Evaluation Funding Future GMP lots Goals Gravid Health Health Care Costs Hour Human Immune system Immunocompromised Host In Situ In Vitro Innovation Corps Iowa Lead Lesion Licensing Malignant Epithelial Cell Malignant Neoplasms Malignant neoplasm of urinary bladder Medical Medical Care Costs Mitomycin C Modeling Monitor Mus Oncologist Organoids Pain Papillary Patients Penetration Performance Pharmaceutical Preparations Pharmacologic Substance Pharmacy facility Phase Pilot Projects Positioning Attribute Private Sector Privatization Process Production Property Recurrence Research Resected Safety Ships Silicon Dioxide Small Business Innovation Research Grant Spasm Specificity Technology Teratogenic effects Testing Therapeutic Time Toxicology Transitional Cell Carcinoma Translating Transurethral Resection United States National Institutes of Health Universities Urination Urology Work base bladder transitional cell carcinoma cGMP production cancer cell cancer therapy canine model chemotherapeutic agent chemotherapy clinically relevant college commercialization contrast imaging cost data acquisition design detrusor muscle docetaxel first-in-human follow-up gemcitabine improved in vitro testing in vivo interest intravesical mouse model nanomaterials nanoparticle neoplastic cell novel novel strategies novel therapeutics off-patent particle preclinical study preclinical trial programs prototype response scale up screening side effect standard care standard of care success tumor tumor growth ultrasound urologic

项目摘要

Project Summary/Abstract: Transitional cell carcinoma (TCC) of the bladder is the fifth most common form of cancer in the U.S., with over 80,000 new cases expected in 2019. For early-stage carcinomas, patients receive intravesical bacillus Calmette-Guerin (BCG) immunotherapy, or transurethral resection of the bladder tumor (TURBT) with intravesical chemotherapy. Both are associated with a high rate of recurrence and eventual progression. BCG fails many patients who are immunocompromised or who experience adverse reactions, while TURBT with chemotherapy fails because the chemotherapeutic agent is not sufficiently retained in the bladder to penetrate lesions that aren’t resected. Thus, there is a need for an improved drug formulation for early-stage (CIS, Ta, T1, T2) TCC capable of 1) penetrating the tumor beyond the superficial cell layers, and 2) increasing the dwell/contact time between the chemotherapeutic agent and the cancer cells. To that end, NanoMedTrix (NMTx) has developed a particle based on mesoporous silica nanoparticles (MSN) that carries known chemotherapeutic agents and is designed to improve their specificity, dwell time, and tumor penetration. Our Phase I SBIR project exceeded our goals and demonstrated the safety and efficacy of the MSN particles in carrying and releasing epirubicin in vivo in a murine TCC orthotopic model and in vitro using cultured human TCC cells. Through our participation in the NIH I-CORPS program we spoke with key opinion leaders (urologic oncologists) in the clinical bladder cancer space. As a result, we are completing our Phase I work using the MSN to deliver clinically relevant doses of gemcitabine, docetaxel, and mitomycin-c in the same model. Following our Phase I success, our Phase II SBIR is designed to complete the acquisition of data required by the FDA for initiation of IND approval of NMTx MSN in human clinical trials. Specific Aim 1 describes the necessary in vitro tasks: optimizing particle chemistry and validating our larger canine model using cultured cells and canine TCC organoids. Specific Aim 2 describes completion of murine orthotopic studies and the start of pre-clinical trials in dogs with spontaneously occurring TCC. Specific Aim 3 lays out our plan for carrying out cGMP synthesis, packaging, and analysis of our IND. Beyond setting the stage for FDA IND approval and first-in-human clinical trials, Phase II completion will strengthen our position with investors/partners in the pharmaceutical industry, with whom we will partner in SBIR Phase IIB, Phase III and beyond to expand clinical trials and ultimately commercialize the technology. We are continuing to work with the urology contacts we made in I-CORPS who are eager to participate in clinical trials, and we have received interest from Pharma companies (Bristol-Myers Squibb, Urovant, and others). Our proprietary technology will provide licensees with improved performance from established chemotherapeutics that have already gone off-patent, thus making our technology attractive both clinically and commercially. Ultimate commercial success of this SBIR work will greatly benefit human health while reducing medical costs.

项目摘要/摘要：膀胱的过渡细胞癌（TCC）是第五大最常见的形式美国的癌症，预计在2019年将有80,000例新病例。对于早期癌，患者接受静脉内芽孢杆菌塞氏菌（BCG）免疫疗法或胸腔切除术肿瘤（TURBT）及其静脉化疗。两者都与较高的复发率有关，并且最终进展。 BCG失败了许多免疫功能低下或遭受不利的患者反应，而与化学疗法的TURBT失败，因为化学治疗剂还不够保留在膀胱中以穿透未切除的病变。那需要改进的药物早期阶段的公式（CIS，TA，T1，T2）TCC能够1）穿透肿瘤以外细胞层和2）增加化学治疗剂和癌细胞之间的住所/接触时间。为此，Nanomedtrix（NMTX）开发了一种基于介孔二氧化硅纳米颗粒（MSN）的粒子它具有已知的化学治疗剂，旨在改善其特异性，停留时间和肿瘤渗透。我们的I阶段SBIR项目超出了我们的目标，并证明了MSN的安全性和效率在鼠TCC原位模型中体内携带和释放表蛋白的颗粒，并在体外使用培养人类TCC细胞。通过参加NIH I-Corps计划，我们与关键意见领导者进行了交谈（泌尿科肿瘤学家）在临床膀胱癌空间中。结果，我们正在完成我使用的阶段我的工作在同一模型中提供临床相关剂量的吉西他滨，多西他赛和丝裂霉素C的MSN。在我们的第一阶段成功之后，我们的第二阶段SBIR旨在完成对数据要求的获取在人类临床试验中启动NMTX MSN IND批准的FDA。特定目标1描述了必要的体外任务：优化颗粒化学并使用培养细胞验证我们的较大犬模型和犬TCC器官。特定目的2描述了鼠正常研究的完成和开始自发发生TCC的狗进行临床前试验。特定目标3规定了我们执行的计划 CGMP合成，包装和我们的IND分析。除了设定FDA IND批准和人类临床试验的阶段，第二阶段完成还将加强与制药行业的投资者/合作伙伴的立场，我们将与他们合作 IIB期，第三阶段及以后扩展临床试验并最终将技术商业化。我们是继续与我们渴望参加临床试验的I-Corps进行的泌尿科联系，我们已经收到了制药公司（Bristol-Myers Squibb，Urovant等）的兴趣。我们的专有技术将为许可提供既定化学治疗剂的绩效的提高这些已经不受欢迎，因此使我们的技术在临床和商业上都具有吸引力。这项SBIR工作的最终商业成功将极大地使人类健康受益，同时降低医疗费用。