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标是开发一种新的治疗方法，以改善患有以下疾病的患者的治疗结果中等风险的前列腺癌。适应症为与放射治疗联合的一线辅助药物用于前列腺癌。期望的结果是提高局部控制率、减少复发和提高无病生存率。这笔赠款将用于开发和评估 ProstAtak”，这是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预后。前列腺癌症是美国男性癌症死亡的第二大原因，约有 30,000 人死亡预期于 2006 年实现。目前的疗法为每年 230,000 名新患者提供了极好的 5 年生存预后诊断。然而，每年有 60,000-100,000 名男性出现前列腺癌复发。接受手术或药物阉割，这是一种延长生命但非治愈性的疗法。消极阉割影响生活质量。减少前列腺癌复发且不会削弱当前成功的药物从标准疗法中获益将具有重大意义。 ProstAtak”是一种生物药物，由带有疱疹胸苷激酶基因 (AdV-tk) 的腺病毒载体，配制用于前列腺递送，然后一种口服抗疱疹前药。当与标准手术或放射治疗相结合时，ProstAtak”已被证明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效果 (GMCI")。AdV-tk 是 ProstAtak" 的主要成分，具有出色的安全性，超过 300 在多项 1 期研究和一项非随机 2 期研究中提供的患者剂量。前列腺癌已显示出对单独使用 ProstAtak 以及在 GMCI 和辐射的情况下均敏感。目的该应用程序旨在支持随机 2 期对照试验的设计、实施和评估 ProstAtak”与放疗相比，在局部中危前列腺癌中放疗的安慰剂。A 泌尿外科、放射治疗、病理学、免疫学和生物统计学顶级专家组成的工作组学术机构已聚集在一起合作开发和开展拟议的研究。该小组的临床方案已准备就绪。中等风险组的选择基于非随机研究的积极结果，区分该患者群体结果的潜力，并且因为此阶段的标准治疗提供了轻松合并 GMCI 的机会”，而无需给患者带来明显的不适。拟议的试验将是第一个前瞻性评估 AdV-tk 在人类中的功效，如果成功，可能会成为第一种治疗早期前列腺癌的药物它的主要适应症。次要目标是前瞻性评估早期阶段的替代终点前列腺癌。