Therapy Evaluation Core

PROJECT DESCRIPTION/ABSTRACT – THERAPY EVALUATION CORE The goal of our Center of Innovation for Brain Tumor Therapeutics is to nominate only the most promising novel treatment strategies for late-stage clinical testing. This will be accomplished through careful pre-clinical evaluation of potential drug candidates for adequate brain tumor distribution, optimization of dose and schedule

for combinatorial regimens, and rigorous efficacy analyses. Combined with careful evaluation of pharmacokinetics (PK) and pharmacodynamics (PD), these studies will be used to establish a PK→PD→efficacy model to predict whether the novel regimen is likely to have adequate distribution and efficacy in human GBM.

These predictions then will be tested in Phase 0/I clinical trials in which the safety, tolerability, drug distribution and on-target effects will be tested. Integration of human PK/PD data into our model then will be used to help inform decision making for whether to move specific novel therapies into more advanced Phase II or III clinical

trial testing. To accomplish this, the Therapy Evaluation Core and the Pharmacology Core will work closely to support the research being performed within the Projects and the broader Glioblastoma Therapeutics Network (GTN). The scope of work for the Therapy Evaluation Core can be categorized in the two aims described below.

Specific Aim 1: Develop, manage and execute in vivo studies in tumor-bearing animals Specific Aim 2: Develop and manage early-phase clinical trial studies