Comparative Oncology Trials Consortium

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

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.