Tissue-Based Trials: Windows of Opportunity in Neuro-Oncology Drug Development.

Tissue-based trials use limited exposure to investigational agents to obtain human tumor pharmacokinetic and pharmacodynamic data early in development. This approach is particularly valuable in neuro-oncology, where preclinical models are imperfect and the blood-brain barrier complicates conventional drug development. Phase 0 and related tissue-based studies directly test whether an agent reaches the tumor, engages its intended target, and elicits the expected biological effect. This chapter describes the rationale and regulatory framework for tissue-based trials, distinguishes the principal designs, and addresses their operational requirements and interpretation.