Clinical and Immunologic Evaluation of ProstAtak for Prostate Cancer

ProstAtak 治疗前列腺癌的临床和免疫学评价

基本信息

批准号：
8240108
负责人：
Estuardo Aguilar-Cordova
金额：
$ 191.76万
依托单位：
ADVANTAGENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-10 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8240108
关键词：
Acute Adenovirus Vector Adjuvant Adverse effects Advisory Committees Affect American Cancer Society Androgens Antigen-Presenting Cells Applications Grants Biometry Biopsy Blood specimen CD8B1 gene Cancer Etiology Cancer Patient Castration Cessation of life Clinical Clinical Protocols Clinical Research Clinical Trials Design Conduct Clinical Trials Control Groups Development Diagnosis Discipline Disease Disease-Free Survival Distant Dose Enrollment Evaluation Failure Freedom Future Genes Grant HSV-Tk Gene Human Immune Immunologics Immunology Immunotherapy Inflammatory Response Institution Institutional Review Boards Lead Life Malignant Neoplasms Malignant neoplasm of prostate Measurable Measures Mediating Modeling Neoplasm Metastasis Operative Surgical Procedures Oral Outcome Pathologic Pathology Patients Performance Pharmaceutical Preparations Phase Phase II Clinical Trials Placebo Control Placebos Population Predisposition Prodrugs Property Prostate Prostate Cancer therapy Prostate-Specific Antigen Protocols documentation Quality of life Radiation Radiation Oncology Radiation therapy Randomized Randomized Controlled Trials Reagent Recombinant DNA Recurrence Research Design Research Methodology Resistance development Resources Risk Safety Site Staging Superantigens Surrogate Endpoint T cell response T-Lymphocyte TK Gene Technology Testing Therapeutic Toxic effect Tumor Antigens United States National Institutes of Health Urology Vaccines Work Writing base cancer recurrence cancer therapy cell killing chemotherapy clinical research site control trial cytotoxic deprivation design experience follow-up high risk implementation trial improved institutional biosafety committee meetings men neoplastic cell novel therapeutics outcome forecast palliative patient population phase 1 study phase 2 study pre-clinical prevent product development randomized placebo controlled trial randomized trial response standard care standard of care success tumor uptake working group

项目摘要

ABSTRACT The main objective of this project is to develop a new therapeutic to improve the outcome for patients with intermediate-risk prostate cancer. The indication is a first-line adjuvant to be combined with radiation therapy for prostate cancer. The desired outcomes are improved local control rate, decreased recurrence and improved disease-free survival. This grant will enable development and evaluation of ProstAtak", a product aimed at improving the outcome of prostate cancer patients, in a randomized Phase 2 clinical study. Prostate cancer is the second leading cause of cancer death in men in the US with approximately 30,000 deaths expected in 2006. Current therapies provide an excellent 5yr survival prognosis for the 230,000 new annual diagnoses. However, each year 60,000-100,000 men develop prostate cancer recurrence for which they receive surgical or pharmacologic castration, a life extending but non-curative therapy. Castration negatively impacts quality of life. Drugs that decrease recurrence of prostate cancer and do not diminish current success from standard therapies would be of great significance. ProstAtak" is a biologic drug composed of an adenoviral vector with the Herpes thymidine-kinase gene (AdV-tk) formulated for prostate delivery followed by an oral antiherpetic prodrug. When combined with standard surgery or radiation, ProstAtak" has been shown to generate a systemic vaccine effect through a technology termed gene mediated cytotoxic immunotherapy (GMCI"). AdV-tk, the principal component of ProstAtak", has an excellent safety profile with over 300 patient doses delivered in multiple Phase 1 studies, and a non-randomized Phase 2 study. Prostate cancer has shown susceptibility to ProstAtak" alone, and in the context of GMCI" with radiation. The purpose of this application is to support design, implementation and evaluation of a randomized Phase 2 controlled trial of ProstAtak" with radiation compared to placebo with radiation in localized intermediate-risk prostate cancer. A working group of urology, radiation therapy, pathology, immunology and biostatistics experts from top academic institutions has been assembled to collaborate in the development and conduct the proposed studies. A clinical protocol from this group has been prepared. The intermediate-risk group was selected based on positive results from the non-randomized study, the potential to differentiate outcomes in this patient population, and because standard treatment for this stage provides an opportunity to easily incorporate GMCI" without adding significant discomfort to the patients. The proposed trial will be the first to prospectively evaluate efficacy of AdV-tk in humans and, if successful, may lead to the first drug with early stage prostate cancer as its primary indication. A secondary objective is to prospectively evaluate surrogate end-points for early stage prostate cancer.

抽象的该项目的主要目的是开发一种新的治疗性，以改善中等风险前列腺癌。该指示是与放射治疗结合的一线辅助前列腺癌。期望的结果是提高了局部控制率，降低的复发率和改善无病生存。该赠款将实现Prostatak的开发和评估”，一种产品在一项随机2期临床研究中，旨在改善前列腺癌患者的结果。前列腺癌症是美国男性癌症死亡的第二大主要原因，死亡约30,000 预计在2006年。当前的疗法为230,000年的年度提供了出色的5年生存预后诊断。但是，每年有60,000-100,000名男性出现前列腺癌复发接受手术或药理学cast割，是一种延长但非耐疗法的生活。 cast割负面的影响生活质量。减少前列腺癌复发并且不会减少当前成功的药物根据标准疗法将具有重要意义。 Prostatak”是一种生物药，由腺病毒载体与疱疹胸苷 - 激酶基因（ADV-TK），用于前列腺递送，然后是口服抗蛇毒前药。当与标准手术或辐射结合使用时，已显示Prostatak” 通过称为基因介导的细胞毒性免疫疗法的技术产生系统性疫苗作用（gmci“）。adv-tk，Prostatak的主要组成部分”，具有出色的安全性，超过300 患者剂量在多个第1期研究中提供，并进行非随机2期研究。前列腺癌在辐射的情况下显示出对前列腺的敏感性。目的此应用是为了支持对2阶段2对照试验的设计，实施和评估 prostatak”与安慰剂相比，与安慰剂相比，局部中等风险前列腺癌的辐射。泌尿外科，放射疗法，病理学，免疫学和生物统计学专家的工作组学术机构已被组成，以合作开发并进行拟议的研究。已经准备了该组的临床方案。根据非随机研究的积极结果，分化该患者人群的结果的潜力，而且由于此阶段的标准治疗提供了一个机会，可以轻松地合并GMCI” 给患者增加了明显的不适。拟议的试验将是第一个预期评估的试验 ADV-TK在人类中的功效，如果成功，可能会导致第一种患有早期前列腺癌的药物它的主要迹象。次要目标是前瞻性评估早期的替代终点前列腺癌。