ProstaFluor FDA Trial for Real-Time Margin Detection During Prostatectomy

ProstaFluor 用于前列腺切除术期间实时边缘检测的 FDA 试验

• 批准号: 8472458
• 负责人: David A. Benaron
• 金额: $ 54.44万
• 依托单位: SPECTROS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-19 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8472458
• 关键词: Abdomen; Adopted; Affect; Animal Model; Animals; Antibodies; Area; Attention; Blood flow; Bone Marrow; Breast; Cancer Detection; Cells; Cessation of life; Clinical; Clinical Research; Clinical Trials; Colon; Contracts; Contrast Media; Data Analyses; Death Rate; Detection; Devices; Diagnosis; Disease; Dose; Drug Formulations; Ductal Epithelial Cell; Dyes; Endoscopes; Enrollment; Excision; FDA approved; Fluorescence; Fluorescent Dyes; Folate; Funding; Glutamate Carboxypeptidase II; Goals; Grant; Greater sac of peritoneum; Health; Human; Image; Imagery; Impotence; Injectable; Injection of therapeutic agent; Institutes; Ischemia; Lead; Left; Luciferases; Lymphatic Spread; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Marketing; Microscope; Monitor; Monoclonal Antibodies; Morbidity - disease rate; Neoplasm Metastasis; Operating Rooms; Operative Surgical Procedures; Optics; Organ; Outcome; PSA Velocity; Pathology; Patients; Pelvis; Perforation; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Pilot Projects; Principal Investigator; Production; Prostate; Prostatectomy; Prostatic; Prostatic Diseases; Prostatic Neoplasms; Publications; Radiation; Radiation therapy; Reagent; Recurrence; Relapse; Research; Residual Cancers; Residual Tumors; Risk; Robotics; Safety; Sales; Selection for Treatments; Silicon Dioxide; Site; Spectrum Analysis; Staging; Surface Antigens; Surface of the Prostate; Surgical margins; Survival Rate; System; TStat; Technology; Testing; Time; Tissues; Toxic effect; United States National Institutes of Health; Urinary Incontinence; Woman; Work; abstracting; antibody conjugate; base; cancer recurrence; cost; design; experience; fluorescence imaging; high risk; human subject; humanized antibody; improved; in vivo; instrument; irradiation; killings; lymph nodes; malignant breast neoplasm; manufacturing scale-up; member; men; millimeter; molecular imaging; monitoring device; mortality; programs; prostate surgery; receptor; research clinical testing; scale up; tool; tumor

DESCRIPTION (provided by applicant): In this 5 year academic-industrial partnership to FDA approval, an experienced team and partners including Cornell, Vanderbilt, Intuitive Surgical, LI COR, and Sand Hill Institute, will move a prostate-targeted fluorescent contrast agent, demonstrated in a prior R44 project to allow real time detection of residual tumor in animals, through FDA approval to human use. The unmet need is that because prostate tumor at the surgical margin is undetectable in real time, residual tumor at the margin occurs in 30% of all prostatectomies. Such patients have a significantly higher risk of local recurrence, metastasis, and death, and also require radiation therapy. In contrast, even patients with extra prostatic extension of tumors do better when the margins are made clean of tumor during surgery. We propose to leverage our experience and our animal proven agent to synthesize, receive FDA IND approval on, and Phase I/II test our targeted fluorescent conjugate in a pilot study in 96 human subjects. Our agent is made from a commercial LICOR fluorescent dye, and a humanized antibody from Cornell and Millennium Pharmaceuticals (huJ-591). The targeted antibody tags all prostate cells of luminal origin, and was demonstrated in prior funding to produce 4-12 fold contrast for prostate cells over nearby tissues in animals. The device will be tested a sites using a fluorescence-sensitive surgery system from Intuitive Surgical, a $10 billion robotic surgery company. The PI of this grant has previously developed and commercialized fundamental optical technologies he (1) co-developed the first in vivo luciferase imaging system at Stanford and co-founded Xenogen, and (2) he developed T- Stat(R), the first FDA approved detection system for insufficient blood flow to tissue. Other team members have synthesized dye conjugates for commercial use, and managed antibody based drug formulation through FDA approval. The corporate partners, LiCor (a world leader in automated sequencing instruments and reagents using near infrared devices and dyes) and Sand Hill Institute (experienced at antibody formulation), and Intuitive Surgical, provide proven commercial translational experience in contrast agents and FDA approval. These groups will formulate and synthesize the agent, leading to FDA IND filing and human clinical testing. Alternative paths minimize risks at each stage. If successful, the commercial dye will be readied for Phase III multi-center trial with a major surgical tool partner, a costly and required path to market introduction. Major imaging companies (Siemens, Phillips, GE, and others) also have molecular imaging programs, into which this contract agent will fit. A successful imaging agent would likely be adopted. Extensions to ovarian cancer using the foliate type II receptor, and other targets, are envisioned, including use with other targeting antibodies developed by other groups. We anticipate that this will be among the first of many real-time surgery-targeting optical contrast agents in human subjects. Areas with immediate application are the detection of lymphatic spread intraoperatively for prostate cancer, as well as for ovarian cancer using a Folate. We expect that the market for such a device in cancer could reasonably be in the hundreds of millions of dollars/year. Form SF-424 Abstract

描述（由申请人提供）：在 FDA 批准的这一为期 5 年的学术-工业合作伙伴关系中，经验丰富的团队和包括康奈尔大学、范德比尔特大学、Intuitive Surgical、LI COR 和 Sand Hill Institute 在内的合作伙伴将开发一种前列腺靶向荧光造影剂，在之前的 R44 项目中证明，可以实时检测动物体内的残留肿瘤，并通过 FDA 批准用于人类。未满足的需求是，由于手术切缘处的前列腺肿瘤无法实时检测到，因此在所有前列腺切除术中，30%的患者会出现切缘残留肿瘤。此类患者局部复发、转移和死亡的风险明显较高，也需要放射治疗。相比之下，即使是肿瘤超出前列腺范围的患者，如果在手术过程中清除了肿瘤边缘，效果也会更好。我们建议利用我们的经验和经过动物验证的试剂来合成我们的目标荧光缀合物，获得 FDA IND 批准，并在 96 名人类受试者的试点研究中进行 I/II 期测试。我们的试剂由商业 LICOR 荧光染料和康奈尔大学和 Millennium Pharmaceuticals 的人源化抗体 (huJ-591) 制成。靶向抗体标记所有管腔来源的前列腺细胞，并在之前的资助中得到证明，可以使动物体内的前列腺细胞与附近组织相比产生 4-12 倍的对比度。该设备将使用 Intuitive Surgical（一家价值 100 亿美元的机器人手术公司）的荧光敏感手术系统进行现场测试。此项资助的 PI 之前开发了基础光学技术并将其商业化，他 (1) 在斯坦福大学共同开发了第一个体内荧光素酶成像系统并共同创立了 Xenogen，(2) 他开发了 T-Stat(R)，这是第一个FDA 批准了组织血流不足的检测系统。其他团队成员合成了用于商业用途的染料缀合物，并通过 FDA 批准管理基于抗体的药物配方。公司合作伙伴 LiCor（使用近红外设备和染料的自动测序仪器和试剂领域的世界领先者）、Sand Hill Institute（在抗体配制方面经验丰富）以及 Intuitive Surgical 在造影剂和 FDA 批准方面提供了经过验证的商业转化经验。这些小组将配制和合成该药物，从而向 FDA 提交 IND 申请并进行人体临床测试。替代路径可以最大限度地减少每个阶段的风险。如果成功，商业染料将准备好与主要手术工具合作伙伴进行 III 期多中心试验，这是一条昂贵且必需的市场推广途径。主要成像公司（西门子、飞利浦、通用电气等）也有分子成像项目，该合同代理将适合其中。可能会采用成功的显像剂。预计使用叶酸 II 型受体和其他靶点扩展到卵巢癌，包括与其他小组开发的其他靶向抗体一起使用。我们预计这将是众多针对人类受试者的实时手术靶向光学造影剂中的第一个。立即应用的领域是使用叶酸检测术中前列腺癌和卵巢癌的淋巴扩散。 我们预计这种癌症设备的市场每年可能达到数亿美元。 SF-424 表格摘要