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: 7943011
• 负责人: Estuardo Aguilar-Cordova
• 金额: $ 190.25万
• 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 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7943011
• 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

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.

描述(由申请人提供)：该项目的主要目标是开发一种新的治疗方法，以改善中等风险前列腺癌患者的预后。该适应症是与前列腺癌放射治疗相结合的一线佐剂。预期的结果是提高局部控制率、减少复发和改善无病生存率。这笔赠款将使ProstAtak(Tm)的开发和评估成为可能，ProstAtak(Tm)是一种旨在改善前列腺癌患者预后的产品，它将在一项随机的第二阶段临床研究中进行开发和评估。前列腺癌是美国男性癌症死亡的第二大原因，预计2006年约有3万人死亡。目前的治疗方法为每年新增的230,000例患者提供了良好的5年生存预后。然而，每年有60,000-100,000名男性前列腺癌复发，他们接受手术或药物去势，这是一种延长生命但无效的治疗方法。阉割对生活质量有负面影响。减少前列腺癌复发并不会削弱目前标准疗法的成功的药物将具有重要意义。ProstAtak(Tm)是一种生物药物，由携带疱疹胸苷激酶基因(ADV-tk)的腺病毒载体组成，用于前列腺癌的递送，然后是口服抗疱疹前药。当与标准手术或放射治疗相结合时，ProstAtak(Tm)已被证明通过一种名为基因介导的细胞毒性免疫疗法(GMCI(Tm))的技术产生系统性疫苗效应。ProstAtak(Tm)的主要成分ADV-tk具有极好的安全性，在多个第一阶段试验和一项非随机第二阶段试验中提供了300多个患者剂量。前列腺癌已经显示出对单独的ProstAtak(Tm)，以及在GMCI(Tm)与辐射的情况下的敏感性。这项申请的目的是支持设计、实施和评估在局部中等风险前列腺癌患者中使用ProstAtak(Tm)与安慰剂进行放射治疗的随机2期对照试验。一个由来自顶尖学术机构的泌尿学、放射治疗、病理学、免疫学和生物统计学专家组成的工作组已经聚集在一起，共同开发和进行拟议的研究。该小组已经准备了一份临床方案。中等风险组的选择是基于非随机研究的积极结果、在这一患者群体中区分结果的可能性，以及因为这一阶段的标准治疗提供了一个机会，可以轻松地纳入GMCI(Tm)，而不会给患者带来明显的不适。这项拟议的试验将首次前瞻性地评估adv-tk在人类中的疗效，如果成功，可能会导致第一种以早期前列腺癌为主要适应症的药物。第二个目标是前瞻性评估早期前列腺癌的替代终点。