Table 2.

Categorizing modern oncology clinical trial designs

Platform trialEvaluates many therapies in a particular disease or group of diseases. Therapies usually have different sponsors and may be combinations or sequences.
Standing trialPlatform trial in which therapies enter and leave over time.
Master protocolA trial with multiple treatment options requiring separate protocols but under the same aegis. Informed consent is usually required for both the master protocol and the respective individual protocol.
Indication finderEvaluates a particular therapy across multiple cancers that are defined by organ type or across subtypes within a specific organ type. The goal is to determine which diseases or which biomarker subtypes are appropriate for further development.
Basket (or bucket) trialEvaluates the effect of a particular targeted therapy on a particular genetic or molecular aberration across cancer organ types. Variant of indication finder but the therapy is not evaluated for its off-target effects.
Umbrella trialThis term may be useless because it is used for very different designs by different researchers and reporters. I use it for platform trials (many therapies) that are indication finders for each therapy.
Adaptive trialTrials in which unblinded data are monitored and used to determine the future course of the trial based on prospectively defined decision rules.
Seamless phasesaA particular kind of adaptive trial that moves from one phase of drug development to another without pausing accrual. Decisions at the phase switch usually involve greater focus. Examples include dropping arms, dropping doses or schedules, dropping patient subsets, changing randomization proportions, estimating the sample size for the next phase, and there are many possibilities. (I do not include changing primary endpoint for reasons indicated in the text.)
  • aFDA's February draft “Guidance for Industry, Adaptive Design Clinical Trials for Drugs and Biologics” (46) is focused on phase III trials. It avoids the term “seamless phase II/III” because the term provides “no additional meaning beyond the term adaptive.”

    Reprinted from ref. 5: Molecular Oncology, Vol 9, Berry DA, The Brave New World of clinical cancer research: adaptive biomarker-driven trials integrating clinical practice with clinical research, 951–9, Copyright 2015, with permission from Federation of European Biochemical Societies.