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

• 批准号: 7274580
• 负责人: Estuardo Aguilar-Cordova
• 金额: $ 10.11万
• 依托单位: ADVANTAGENE, INC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-10 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7274580
• 关键词: Acute; Address; Adenovirus Vector; Adjuvant; Adverse effects; Advisory Committees; Affect; American Cancer Society; Androgens; Antigen-Presenting Cells; Appendix; Applications Grants; Biometry; Biopsy; Blood specimen; CD8B1 gene; Cancer Etiology; Cancer Patient; Caring; Castration; Cessation of life; Clinical; Clinical Protocols; Clinical Research; Conduct Clinical Trials; Control Groups; Development; Diagnosis; Discipline; Disease; Disease-Free Survival; Distant; Dose; Early Diagnosis; End Point; Enrollment; Evaluation; Failure; Freedom; Future; Genes; Grant; HSV-Tk Gene; Human; Immune; Immunologics; Immunology; Immunotherapy; Individual; Inflammatory Response; Institution; Lead; Life; Localized; Malignant Neoplasms; Malignant neoplasm of prostate; Measurable; Measures; Mediating; Methods; Modeling; Morbidity - disease rate; Neoplasm Metastasis; Operative Surgical Procedures; Oral; Outcome; Pathologic; Pathology; Patients; Performance; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Placebo Control; Placebos; Population; Predisposition; Prodrugs; Productivity; Property; Prostate; Prostate Cancer therapy; Prostate-Specific Antigen; Protocols documentation; Purpose; Quality of life; Radiation; Radiation Oncology; Radiation therapy; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Rate; Reagent; Recombinant DNA; Recurrence; Research Design; Research Ethics Committees; Resistance development; Resources; Risk; Safety; Site; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Societies; Staging; Standards of Weights and Measures; Superantigens; Surrogate Endpoint; T-Lymphocyte; TK Gene; Technology; Testing; Therapeutic; Time; Toxic effect; Translating; Tumor Antigens; United States Food and Drug Administration; United States National Institutes of Health; Urology; Vaccines; Work; Writing; base; cancer recurrence; cancer therapy; cell killing; chemotherapy; clinical research site; cost; cytotoxic; deprivation; design; desire; disease natural history; experience; follow-up; implementation trial; improved; men; neoplastic cell; novel therapeutics; outcome forecast; pre-clinical; prevent; randomized placebo controlled trial; response; success; therapy development; tumor; uptake; Acute; Address; Adenovirus Vector; Adjuvant; Adverse effects; Advisory Committees; Affect; American Cancer Society; Androgens; Antigen-Presenting Cells; Appendix; Applications Grants; Biometry; Biopsy; Blood specimen; CD8B1 gene; Cancer Etiology; Cancer Patient; Caring; Castration; Cessation of life; Clinical; Clinical Protocols; Clinical Research; Conduct Clinical Trials; Control Groups; Development; Diagnosis; Discipline; Disease; Disease-Free Survival; Distant; Dose; Early Diagnosis; End Point; Enrollment; Evaluation; Failure; Freedom; Future; Genes; Grant; HSV-Tk Gene; Human; Immune; Immunologics; Immunology; Immunotherapy; Individual; Inflammatory Response; Institution; Lead; Life; Localized; Malignant Neoplasms; Malignant neoplasm of prostate; Measurable; Measures; Mediating; Methods; Modeling; Morbidity - disease rate; Neoplasm Metastasis; Operative Surgical Procedures; Oral; Outcome; Pathologic; Pathology; Patients; Performance; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Placebo Control; Placebos; Population; Predisposition; Prodrugs; Productivity; Property; Prostate; Prostate Cancer therapy; Prostate-Specific Antigen; Protocols documentation; Purpose; Quality of life; Radiation; Radiation Oncology; Radiation therapy; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Rate; Reagent; Recombinant DNA; Recurrence; Research Design; Research Ethics Committees; Resistance development; Resources; Risk; Safety; Site; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Societies; Staging; Standards of Weights and Measures; Superantigens; Surrogate Endpoint; T-Lymphocyte; TK Gene; Technology; Testing; Therapeutic; Time; Toxic effect; Translating; Tumor Antigens; United States Food and Drug Administration; United States National Institutes of Health; Urology; Vaccines; Work; Writing; base; cancer recurrence; cancer therapy; cell killing; chemotherapy; clinical research site; cost; cytotoxic; deprivation; design; desire; disease natural history; experience; follow-up; implementation trial; improved; men; neoplastic cell; novel therapeutics; outcome forecast; pre-clinical; prevent; randomized placebo controlled trial; response; success; therapy development; tumor; uptake

DESCRIPTION (provided by applicant): 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(tm), 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(tm) 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(tm) has been shown to generate a systemic vaccine effect through a technology termed gene mediated cytotoxic immunotherapy (GMCI(tm)). AdV-tk, the principal component of ProstAtak(tm), 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(tm) alone, and in the context of GMCI(tm) with radiation. The purpose of this application is to support design, implementation and evaluation of a randomized Phase 2 controlled trial of ProstAtak(tm) 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(tm) 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. Prostate cancer recurrence is a growing problem in the US due to earlier diagnosis and increased use of life-extending, non-curative therapies. The American Cancer Society estimates that in 2006 there will be 230,000 new cases, 60,000-100,000 recurrences, and 30,000 deaths from prostate cancer. Upon recurrence, the treatment is surgical or pharmacologic castration, which is non-curative and associated with significant morbidity. Usually by the time of death, men have been suffering from prostate cancer recurrence and the side effects of treatments for over 10 years. The costs to individuals and society of treatment, lost productivity and compromised quality of life due to recurrence are a huge problem, which needs to be addressed with new more effective and less toxic therapies. The main objective of this SBIR project is to develop a new therapeutic to improve the outcome for patients with intermediate-risk prostate cancer. This grant will enable evaluation of ProstAtak(tm), a product aimed at improving the outcome of prostate cancer patients, in a randomized Phase 2 clinical study. In addition, a secondary objective is to prospectively evaluate surrogate end-points for early stage prostate cancer. There are no approved drugs with early stage prostate cancer as their primary indication; ProstAtak(tm) would be a first. This is in part due to the prolonged natural history of the disease, which translates into prohibitory long clinical development times. The availability of validated shorter-term surrogate end-points would significantly impact the overall approach of therapy development for this disease.

描述（由申请人提供）：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患者的结果。该适应症是将前列腺癌放射治疗结合使用的一线佐剂。预期的结果是提高了局部控制率，降低了复发和改善无疾病的生存率。在一项随机2期临床研究中，该赠款将使Prostatak（TM）的开发和评估旨在改善前列腺癌患者的结果。前列腺癌是美国男性癌症死亡的第二大主要原因，预计在2006年死亡约30,000例。当前的疗法为230,000个新的年度诊断提供了出色的5年生存预后。但是，每年有60,000-100,000名男性出现前列腺癌复发，他们接受了手术或药物cast割，这是一种延长但非持续治疗的生活。 cast割对生活质量产生负面影响。降低前列腺癌复发并不会减少标准疗法的当前成功的药物将具有重要意义。 Prostatak（TM）是一种由腺病毒载体组成的生物学药物，其疱疹胸腺苷基因基因（ADV-TK）用于前列腺递送，然后是口服抗抗凝治前药。当与标准手术或放射线结合使用时，Prostatak（TM）已显示通过称为基因介导的细胞毒性免疫疗法（GMCI（TM））的技术产生全身疫苗作用。 Prostatak（TM）的主要组成部分Adv-TK具有出色的安全性，在多个1期研究中提供了300多个患者剂量，以及一项非随机2期研究。前列腺癌已显示出对Prostatak（TM）的敏感性，并且在GMCI（TM）的背景下具有辐射。本应用的目的是支持Prostatak（TM）的随机2对照试验的设计，实施和评估，其辐射与安慰剂在局部中等风险前列腺癌中具有辐射相比。来自顶级学术机构的泌尿外科，放射疗法，病理学，免疫学和生物统计学专家的工作组已组装在开发中并进行拟议研究。已经准备了该组的临床方案。根据非随机研究的积极结果选择了中等风险组，这是区分该患者人群的预期的潜力，并且因为此阶段的标准治疗方法提供了一个机会，可以轻松地纳入GMCI（TM）而不给患者增加明显的不适感。拟议的试验将是第一个预期评估Adv-TK在人类中的疗效的试验，如果成功的话，可能会导致第一种患有早期前列腺癌的药物作为其主要的指示。次要目标是预期评估早期前列腺癌的替代终点。由于较早的诊断并增加了延长生命的非疗法疗法，前列腺癌复发是美国日益增长的问题。美国癌症协会估计，在2006年，将有23万例新病例，60,000-100,000例复发和30,000例前列腺癌死亡。复发后，该治疗是手术或药物cast割，这是非垂直性的，并且与明显的发病率有关。通常，到死亡时，男人已经患有前列腺癌复发和治疗的副作用已有10多年了。由于复发而导致的治疗，生产力失去和生活质量的成本是一个巨大的问题，需要使用新的更有效和毒性疗法来解决。该SBIR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患者的结果。在一项随机2期临床研究中，该赠款将使Prostatak（TM）评估Prostatak（TM），该产品旨在改善前列腺癌患者的结果。此外，次要目标是前瞻性评估早期前列腺癌的替代终点。没有批准的患有早期前列腺癌的药物作为其主要迹象。 Prostatak（TM）将是第一个。这部分是由于该疾病的自然历史延长，这转化为禁止的长期临床发育时间。经过验证的短期替代终点的可用性将显着影响该疾病治疗开发的整体方法。