Although Phase 1 studies in most therapeutic areas consist of healthy patients, Phase 1 studies in oncology consist of patients with active disease. This creates unique challenges and potential opportunities. Understanding these challenges and opportunities is paramount for designing Phase 1 oncology studies and keeping them on track.

The goal of Phase 1 studies is to find the optimal dose of therapy, meaning one that is high enough to be effective but not so high as to cause intolerability. Historically, Phase 1 clinical trial designs involved conservative methods of finding maximum tolerated doses. Doses were started at 0. 1 mouse-equivalents, which means 10% of dose that 10% of mice would die from. “Slow-as-you-go” 3 + 3 designs were common. Each dose level would have 3 patients. If patients at one dose level had no dose-limiting toxicity, the next cohort was initiated at a higher dose level. If a cohort met predefined criteria for a dose-limiting toxicity, 3 more patients would be added to the cohort to determine if the event was an outlier or represented a trend. If a drug continued to Phase 2, it would be at the dose level just prior to the one where a dose-limiting toxicity was seen.

Having an approach that is too conservative can lead to trials in which patients are treated with doses too low to be effective (Eisenhauer et al, 2000). This means diseased and sometimes terminally ill patients would be treated with a drug unlikely to be effective. This can be unsettling to the physicians treating patients, and it has raised concern among ethicists. As more targeted therapies are being developed, the focus of Phase 1 trials is shifting toward finding whether a drug is reaching its target tissue or is the optimal biologically active dose. For example, the right dose of a biological like a monoclonal antibody is not necessarily the maximally tolerated dose of this monoclonal but the dose with a saturation of its target.

If you want to learn more about how: Developing a solid trial design, Technology integration and selecting high-performing sites and personnel can help streamline the conduct of your Phase 1 oncology trial and improve the quality of your trial data, download a copy of our whitepaper entitled, “Ensuring Success in Early Phase Oncology Clinical Trials,” at

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