Revolutionary Phase I trial design speeds up development
development, enabling innovative drugs to get to market faster and
cheaper.
Dr Daniel Von Hoff, the chief scientific officer for the US Oncology Research Network, outlined his plan for a 'Complete Phase Ib clinical trial' at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO), held in Chicago this week. The study tested the hypothesis that within a single protocol, several combination phase I trials could be conducted simultaneously. In the current climate of rising R&D costs, increased drug failures and a subsequent reduction in truly innovative drugs, anything that can get new drugs to market faster - or enable no-go decisions earlier in the process - would be warmly welcomed by the pharmaceutical industry. As pharma firms increasingly outsource parts of the development process, the news could also affect service companies within the industry. The usual clinical development plan for a new agent (NA) includes a Phase I monotherapy trial. However, because many new agents are eventually developed as part of a combination of drugs, additional Phase I trials are usually performed too, which assess the drug in combination with established, standard agents (SA). This is usually done as individual phase Ib studies. Which marketed drugs should be studied in combination, is decided through preclinical testing of the new drug. In this new approach, the NA is given to a patient with advanced cancer in combination with a choice of SAs: a tubulin interactive agent; an antimetabolite; an angiogenesis inhibitor; or an antibody to epidermal growth factor receptor (EGFR). Which is used depends on which the clinician believes will be the most suitable for that patient. To test the design, the SA is started at full dose with three patients placed on a one-third dose of NA, three patients on a two-thirds dose of NA, and three to six patients at full dose of the NA. The trial then examines the additive properties of different combinations of drugs, ensuring that the use of two drugs together had no detrimental effects. The 'Complete Phase Ib trial' approach has several advantages over more traditional designs: preclinical data is followed-up very rapidly and in one study; it is cheaper and faster to initiate; patients can be recruited rapidly as many are likely to be eligible considering the SA would be the current standard of care; patients are lesss likely to have already been treated with another drug, which can cause complications in recruitment and analysis of results; the data enables a more informed selection of subsequent phase II or III trials. Dr Von Hoff concluded this new approach is feasible, safe and highly efficient. He said: "Our US Oncology research team is confident that the methodology described in our poster will significantly shorten the time it takes to bring new therapies into the daily care for patients with cancer." Studies using this design are currently being conducted through the network's innovative Translational Oncology Program (TOP). TOP is unique because it conducts early phase trials in a community setting, instead of in academic medical centres. The TOP was founded in 2004 following a request from physicians affiliated with US Oncology to establish an early phase study program. It is comprised of a select group of physicians who examine standard Phase I study design and select Phase II studies, with the goal of establishing a Phase I infrastructure, and eventually incorpoarating targeted cancer drugs. The first study began in March 2005. "What's exciting is that as TOP has evolved, the US Oncology Research Network has taken on more Phase I and II trials that are typically the newest, and often, the most novel approaches to cancer treatment that will ultimately benefit our patients," said Jeffery Nieves, director of the TOP. "Early-stage trials conducted in a smaller, community setting can result in a speedier determination of a new agent's viability, eventually bringing new therapies to patients quicker." With industry players sure to look into this innovative approach to clinical research, if it means more drugs on the market faster, and possibly cheaper, patients will be hoping it proves popular with decision makers.
