Brain Malignancy Steering Committee clinical trials planning workshop: report from the Targeted Therapies Working Group

Abstract

Glioblastoma is the most common primary brain malignancy and is associated with poor prognosis despite aggressive local and systemic therapy, which is related to a paucity of viable treatment options in both the newly diagnosed and recurrent settings. Even so, the rapidly increasing number of targeted therapies being evaluated in oncology clinical trials offers hope for the future. Given the broad range of possibilities for future trials, the Brain Malignancy Steering Committee convened a clinical trials planning meeting that was held at the Udvar-Hazy Center in Chantilly, Virginia, on September 19 and 20, 2013. This manuscript reports the deliberations leading up to the event from the Targeted Therapies Working Group and the results of the meeting.

Keywords: adaptive randomization; biomarkers; clinical trials; glioblastoma.

Fig. 1.

Potential interactions between biomarker-defined subgroups and experimental therapies. Numbers in the boxes are unitless and are used solely to illustrate hypothetical relative treatment effects but may represent data such as median survival in this simplified model.

Fig. 2.

Proposed clinical trial schema. Randomization would initially be balanced, but would ultimately be adapted based on accumulating survival data relating to different biomarker/therapeutic groups. Overall survival would form the foundation of the endpoint, but other factors such as progression and clinical status that were found to be associated with survival during the course of the study would be leveraged to provide earlier, additional information.