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，将制药和生物技术公司等研究赞助商与北美24个学术兽医中心联合起来，以支持研究治疗学的多中心临床试验，其中由NCI提供集中的试验支持和数据管理。这一临床试验基础设施支持将患有癌症的宠物狗整合到抗癌新药的开发路径中。COTC与其他NCI调查人员、学术机构和/或制药业合作，启动宠物动物试验。这些审判是通过联合体成员与COTC成员机构通过单一谅解备忘录联合起来的集体案件量来实施的。这些试验通常规模较小，侧重于与药物开发相关的相关生物终点。宠物动物试验旨在回答有关药物性质的具体问题，赞助商将迅速将结果纳入新型治疗剂的开发计划。通过这些研究产生的数据可供COTC成员使用，以促进由研究人员发起的更大规模的宠物动物试验，这可能进一步补充这一转换过程。缔约方会议提供对审判的领导、监督和管理。试验赞助商，通常是制药公司，支持COTC进行的研究的临床成本。这种支持由赞助商通过集体定义的合同直接支付给COTC中心，这一过程已经简化，不会对试验造成障碍。一项要求是必须在议定书中明确和清楚地说明与人类药物开发有关的科学问题。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一过程。COTC进行的试验旨在包括临床和生物终点，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，并帮助在早期和后期人体试验之间进行困难的过渡。试验的启动和科学发展过程由缔约方会议领导，但涉及与试验赞助商和COTC调查员进行详细和反复的讨论。现有的在COTC内实施试验的基础设施是针对CCR内的现有结构而利用的。例如，我们与Jeff Shling/Pamela Asangong(CCR)合作，维护了CCR的C3D(甲骨文临床)数据报告系统的“狗友好型”版本。这允许COTC研究人员和赞助商在良好临床实践(GCP)下进行实时数据录入和审查，完全类似于人体试验中使用的形式。这使赞助商能够快速评估研究结果，并将其用于FDA提交的文件。第一个完成的COTC试验于2009年发布，第30个试验概念目前开放招生。COTC研究的细节和科学严谨性在我们的试验方案中得到了例证。我们开放试验方案的例子在第五节/临床方案摘要中提供。尽管在比较肿瘤学领域取得了进展，但在自然发展为癌症并与人类癌症有强烈相似之处的大型动物中评估新疗法的概念仍被认为是新的。该领域的一个重要需求是向不同的利益相关者展示这个机会、它的风险和潜在的回报，尤其是制药。并非所有问题都应该或可以通过这种方法提出，因此，缔约方会议在管理这些资源方面发挥了重要作用。这一专门知识最近以《临床癌症研究展望》文章的形式传播，阐述了比较肿瘤学研究的问题和相关价值，以及《自然·癌症评论》的特邀评论。在具体的临床试验活动方面，我们最近公布了Morris动物基金会试验的结果，该试验评估了辅助mTOR抑制作为犬骨肉瘤抗转移方法的效果，以及NCI赞助的3种新型TOP1抑制剂治疗犬淋巴瘤的临床试验。该出版物的结果直接影响并通知了IND提交的在人类第一阶段环境中对这些药物进行评估的申请。最后，我们最近与我们的外部COTC调查人员团队合作，发布了不良事件兽医通用术语标准(V-CTCAE)的更新版，以协调在我们计划内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.