Comparative Oncology Trials Consortium

比较肿瘤学试验联盟

• 批准号: 10926715
• 负责人: Amy Leblanc
• 金额: $ 11.38万
• 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/10926715
• 关键词: Address; Adjuvant; Animals; Antineoplastic Agents; Biological; Biotechnology; CCR; Cancer Biology; Canis familiaris; Clinical; Clinical Protocols; Clinical Trials; Collaborations; Common Terminology Criteria for Adverse Events; Communities; Complement; Complement 3d; Conceptions; Contracts; Data; Data Reporting; Development; Development Plans; Drug Industry; Enrollment; Extramural Activities; Foundations; Friends; Goals; Good Clinical Practice; Human; Infrastructure; Institution; 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; Translation Process; Update; Veterinary Schools; Work; anticancer research; 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)，该联盟是一个基础设施，将制药和生物技术公司等研究申办者与北美 24 个学术兽医中心联合起来，支持研究疗法的多中心临床试验，其中集中试验支持和数据管理由 NCI 提供。这一临床试验基础设施支持将患有癌症的宠物狗纳入新抗癌药物的开发路径。 COTC 与其他 NCI 研究人员、学术机构和/或制药行业合作启动宠物动物试验。这些试验是通过联盟成员与 COTC 成员机构通过一份谅解备忘录 (MOU) 联合起来的集体案例来实施的。这些试验通常规模较小，重点关注与药物开发相关的生物学终点。宠物动物试验旨在回答有关药物特性的具体问题，申办者将迅速将结果纳入新型治疗药物的开发计划中。通过这些研究生成的数据可供 COTC 成员使用，以促进研究者发起的更大规模的宠物动物试验，从而进一步补充这一转化过程。 COP 负责试验的领导、监督和管理。试验申办者（通常是制药公司）支持 COTC 进行的研究的临床费用。这种支持由申办者通过集体定义的合同直接支付给 COTC 中心，并且这一流程已经过简化，不会对试验造成障碍。一项要求是，与人类药物开发相关的科学问题必须在方案中明确、清楚地说明。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 研究人员进行详细和反复的讨论。 COTC 内用于实施试验的现有基础设施可与 CCR 内的现有结构相结合。例如，我们与 Jeff Shilling/Pamela Asangong (CCR) 合作，维护 CCR 的 C3D (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相似。这使得申办者能够快速评估研究结果并在 FDA 提交文件中使用它们。第一个完整的 COTC 试验于 2009 年发布，第 30 个试验概念目前正在开放招募。 COTC 研究要求的细节和科学严谨性在我们的试验方案中得到了例证。我们的开放试验方案的示例在第五节/临床方案摘要中提供。尽管比较肿瘤学领域取得了进展，但在自然发生癌症且与人类癌症具有很强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个利益相关者（尤其是制药行业）展示这一机会、风险和潜在回报。并非所有问题都应该或可以通过这种方法提出，因此 COP 在提供这些资源的管理方面发挥着重要作用。这种专业知识最近以《临床癌症研究》中的一篇观点文章的形式传播，该文章探讨了比较肿瘤学研究的问题和相关价值，以及《自然评论癌症》中的邀请评论。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 赞助的 3 种新型 TOP1 抑制剂在犬中的临床试验淋巴瘤。该出版物的结果直接影响并通知了这些药物在人类第一阶段环境中进行评估的 IND 提交。最后，我们最近与校外 COTC 研究人员团队合作，发布了兽医不良事件通用术语标准 (V-CTCAE) 的更新版本，以统一我们项目和整个社区进行的比较肿瘤学研究的 AE 报告标准。