Comparative Oncology Trials Consortium

比较肿瘤学试验联盟

• 批准号: 10703135
• 负责人: Amy Leblanc
• 金额: $ 10.86万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703135
• 关键词: Address; Adjuvant; Animals; Antineoplastic Agents; Biological; Biotechnology; CCR; Cancer Biology; Canis familiaris; Clinical; Clinical Data; Clinical Protocols; Clinical Trials; Collaborations; Common Terminology Criteria for Adverse Events; Communities; Complement; Conceptions; Contracts; Data; Data Reporting; Development; Development Plans; Drug Industry; Enrollment; Extramural Activities; Foundations; Goals; Good Clinical Practice; Human; Infrastructure; Institution; Investigation; Leadership; Lymphoma; Malignant Neoplasms; Multi-Institutional Clinical Trial; Nature; North America; Oncologist; Oncology; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Play; Positioning Attribute; Process; Property; Protocols documentation; Publications; Publishing; Reporting; Research Personnel; Resources; Rewards; Risk; Role; Structure; System; TOP1 gene; Therapeutic; Therapeutic Agents; Time; Update; Veterinary Schools; Work; anticancer research; base; bridge program; cancer clinical trial; catalyst; comparative; cost; data management; design; drug development; inhibitor; mTOR inhibition; member; novel; novel anticancer drug; novel therapeutics; oncology program; oncology trial; osteosarcoma; pet animal; pharmacokinetics and pharmacodynamics; programs

The core component of the COP is the Comparative Oncology Trials Consortium (NCI-COTC), which is an infrastructure uniting study sponsors, such as pharmaceutical and biotechnology companies, with 24 academic veterinary centers within North America to support multicenter clinical trials of investigational therapeutics, wherein centralized trial support and data management is provided by the NCI. This clinical trial infrastructure supports the integration of pet dogs with cancer into the development path of new cancer drugs. The COTC initiates pet animal trials in collaboration with other NCI investigators, academic institutions and/or the pharmaceutical industry. These trials are implemented through the collective caseloads of the consortium membership with COTC member institutions united through a single Memorandum of Understanding (MOU). These trials are typically small and focused on relevant biological endpoints associated with drug development. The pet animal trials are intended to answer specific questions regarding the properties of a drug and results are to be rapidly integrated into the development plans for novel therapeutic agents by the sponsor. The data generated through these studies are available to COTC members to facilitate larger investigator-initiated pet animal trials that may further complement this translational process. The COP provides leadership, oversight, and management of trials. Trial sponsors, most often pharmaceutical companies, support the clinical costs of studies conducted by the COTC. This support is paid directly to COTC centers by the sponsor through collectively defined contracts, and this process has been streamlined so as to not create a barrier to the trial. A requirement is that the scientific question related to human drug development must be explicitly and clearly stated in the protocol. Due to the unique positioning of the COP, the framework of these questions is usually guided by the COP as many outside investigators are unfamiliar with this process. Trials conducted by the COTC are designed to include clinical and biological endpoints, i.e. pharmacokinetics and pharmacodynamics, so as to optimally inform the design of early phase human trials and assist in the difficult transitions between early and later phase human trials. The process of trial initiation and scientific development is led by the COP but involves detailed and iterative discussions with the trial sponsor and COTC investigators. The infrastructure that exists to implement trials within the COTC is leveraged against existing structures within the CCR. For example, in collaboration with Jeff Shilling/Pamela Asangong (CCR), we maintain a "dog friendly" version of the CCR's C3D (Oracle Clinical) data reporting system. This allows real-time data entry and review under Good Clinical Practice (GCP) by COTC investigators and sponsors exactly analogous to the forms used in human trials. This enables sponsors to quickly assess study results and use them in FDA submissions. The first completed COTC trial was published in 2009 and the 30th trial concept is currently open for enrollment. The detail and scientific rigor mandated for COTC studies is exemplified in our trial protocols. Examples of our open trial protocols are provided under Section V/Clinical Protocol Summary. Despite the progress made in the field of comparative oncology, the concept of evaluating new therapeutics in large animals that naturally develop cancer and share strong similarities to human cancers is still considered novel. A significant need in the field is to present this opportunity, its risks, and potential rewards to various stakeholders, not least of which is Pharma. Not all questions should or can be asked through this approach and thus COP plays an important role in providing stewardship over these resources. This expertise has recently been disseminated in the form of a Perspectives piece in Clinical Cancer Research addressing the questions and associated value of comparative oncology studies, as well as an invited review in Nature Reviews Cancer. With regard to specific clinical trial activities, we recently published the results of a Morris Animal Foundation trial that evaluated adjuvant mTOR inhibition as an anti-metastatic approach in canine osteosarcoma, as well as an NCI-sponsored clinical trial of 3 novel TOP1 inhibitors in canine lymphoma. The results of this publication directly impacted and informed the IND submissions for these agents to be assessed in the human Phase 1 setting. Finally, we recently worked with our team of extramural COTC investigators to publish an updated version of the Veterinary Common Terminology Criteria for Adverse Events (V-CTCAE) to harmonize standard for AE reporting across comparative oncology studies conducted in our program and across the community.

COP的核心组成部分是比较肿瘤学试验联盟（NCI-COTC）， 这是一个基础设施，将研究赞助商，如制药和生物技术， 公司，在北美有24个学术兽医中心，以支持多中心 研究性治疗药物的临床试验，其中集中试验支持和数据 管理由NCI提供。该临床试验基础设施支持整合 宠物狗患癌症的研究进入新的癌症药物的开发道路。COTC发起宠物 与其他NCI研究人员，学术机构和/或 医药行业。这些审判是通过法庭的集体案件进行的。 与COTC成员机构通过单一备忘录联合的联盟成员资格， 谅解备忘录。这些试验通常规模较小，侧重于相关的生物学 与药物开发相关的终点。宠物试验的目的是回答 关于药物特性和结果的具体问题将被快速整合 纳入申办者的新型治疗药物开发计划。生成的数据 通过这些研究，COTC成员可以促进更大的 制造商发起的宠物动物试验，可能进一步补充这一翻译 过程缔约方会议负责领导、监督和管理审判工作。试验申办者， 大多数情况下，制药公司，支持临床研究的费用， COTC。该支持由申办者通过集体方式直接支付给COTC中心 定义的合同，这一过程已经简化，以便不创造障碍， 审判一个要求是，与人类药物开发有关的科学问题必须是 在方案中明确和清晰地说明。由于缔约方会议的独特定位， 这些问题的框架通常由缔约方会议指导，因为许多外部调查人员 不熟悉这个过程。COTC进行的试验旨在包括临床试验， 和生物学终点，即药代动力学和药效学，以便最佳地 为早期人体试验的设计提供信息， 早期和后期的人体试验。审判启动和科学发展的过程 由COP领导，但涉及与试验申办者进行详细和反复的讨论， COTC调查员。在COTC内实施试验的现有基础设施是 利用CCR内的现有结构。例如，与杰夫合作， Shilling/Pamela Asangong（CCR），我们维护CCR的C3 D（Oracle）的“狗友好”版本 临床）数据报告系统。这允许实时数据输入和审查下良好的 COTC研究者和申办者的临床实践（GCP）与所用表格完全相似 在人体试验中。这使申办者能够快速评估研究结果并将其用于FDA 意见书。第一个完成的COTC试验于2009年发表，第30个试验概念 目前正在接受报名。COTC研究要求的细节和科学严谨性是 在我们的试验方案中得到了体现我们的公开试验方案的示例见 第V节/临床方案总结。尽管在比较教育领域取得了进展， 肿瘤学，在自然发育的大型动物中评估新疗法的概念 与人类癌症有很强的相似性的癌症仍然被认为是新的。显著 在这个领域需要的是提出这个机会，它的风险，和潜在的回报，以各种 利益相关者，尤其是制药公司。不是所有的问题都应该或可以通过 这种方法，因此缔约方会议在提供这些管理方面发挥着重要作用， 资源这一专门知识最近以《观点》的形式传播 在临床癌症研究中，解决比较的问题和相关价值， 肿瘤学研究，以及自然评论癌症的邀请评论。关于 具体的临床试验活动，我们最近发表了莫里斯动物的结果， 评估辅助mTOR抑制作为抗转移方法的基础试验， 犬骨肉瘤，以及一项由NCI赞助的3种新型TOP1抑制剂的临床试验， 犬淋巴瘤该出版物的结果直接影响并告知IND 提交这些药物在人类1期环境中进行评估。最后，我们最近 与我们的校外COTC调查员团队合作，发布了 兽医不良事件通用术语标准（V-CTCAE），以协调 在我们的项目中进行的比较肿瘤学研究和 社区