Comparative Oncology Trials Consortium

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）与北美24个学术兽医中心联合起来，以支持研究治疗的多中心临床试验，其中集中试验支持和数据管理由NCI提供。这种临床试验基础设施支持将患有癌症的宠物狗纳入新癌症药物的开发道路。COTC与其他NCI调查人员，学术机构和/或制药行业合作启动宠物动物试验。这些试验是通过联合体成员与COTC成员机构的集体案例来实施的，这些机构通过一份谅解备忘录联合起来。这些试验通常规模较小，重点关注与药物开发相关的相关生物学终点。宠物动物试验旨在回答有关药物性质的具体问题，申办方将迅速将结果纳入新型治疗药物的开发计划中。通过这些研究产生的数据可供COTC成员使用，以促进更大规模的宠物动物试验，这些试验可能进一步补充这一转化过程。缔约方会议负责领导、监督和管理审判工作。试验赞助商，通常是制药公司，支持COTC进行的研究的临床费用。申办者通过集体定义的合同直接向COTC中心支付该支持，该流程已被简化，以免对试验造成障碍。一项要求是，必须在方案中明确和清楚地说明与人用药物开发相关的科学问题。由于缔约方会议的独特地位，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一进程。COTC进行的试验旨在包括临床和生物学终点，即药代动力学和药效学，以便为早期人体试验的设计提供最佳信息，并协助早期和后期人体试验之间的困难过渡。试验启动和科学开发的过程由COP领导，但涉及与试验申办者和COTC研究者的详细和反复讨论。在COTC内实施试验的现有基础设施与CCR内的现有结构相匹配。例如，我们与Jeff Shilling/Pamela Asangong（CCR）合作，维护CCR的C3 D（Oracle Clinical）数据报告系统的“狗友好”版本。这允许COTC研究者和申办者根据良好临床实践（GCP）进行实时数据输入和审查，与人体试验中使用的表格完全类似。这使申办者能够快速评估研究结果，并在FDA申报中使用这些结果。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开放招募。COTC研究的细节和科学严谨性在我们的试验方案中得到了体现。我们的开放试验方案示例见第V节/临床方案总结。尽管在比较肿瘤学领域取得了进展，但在自然发生癌症并与人类癌症具有强烈相似性的大型动物中评估新疗法的概念仍然被认为是新颖的。该领域的一个重要需求是向各种利益相关者展示这一机会、其风险和潜在回报，尤其是制药公司。并非所有问题都应该或可以通过这种方式提出，因此缔约方会议在管理这些资源方面发挥着重要作用。这种专业知识最近以临床癌症研究的观点的形式传播，解决了比较肿瘤学研究的问题和相关价值，以及Nature Reviews Cancer的特邀评论。关于具体的临床试验活动，我们最近发表了莫里斯动物基金会试验的结果，该试验评估了辅助mTOR抑制作为犬骨肉瘤的抗转移方法，以及NCI申办的3种新型TOP1抑制剂在犬淋巴瘤中的临床试验。该出版物的结果直接影响并告知了这些药物在人体I期环境中评估的IND提交。最后，我们最近与我们的校外COTC研究者团队合作，发布了兽医不良事件通用术语标准（V-CTCAE）的更新版本，以协调在我们项目和整个社区进行的比较肿瘤学研究中的AE报告标准。

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.