Window-of-opportunity trials to evaluate clinical activity of new molecular entities in oncology.

Background: The introduction of molecular targeted agents (e.g., monoclonal antibodies or kinase inhibitors) and cancer vaccines has raised the question whether alternate clinical trial designs, including window trials, are better suited to evaluate such new molecular entities (NMEs) and improve their approval rates. In window trials, patients receive an NME for a window of time before starting standard treatment allowing the evaluation of an NME in tumors unperturbed by previous therapies.

Methods: A systematic literature search was conducted to identify window trials in adult and pediatric oncology.

Results: Twenty-nine window trials were identified and reviewed, 13 in pediatric and 16 in adult oncology. Most of the trials (20/29) tested cytotoxics known to have activity in other clinical situations. In contrast to trials with pretreated patients, the window trials established the antitumor activity of melphalan, topotecan, epirubicin and etoposide in untreated patients with rhabdomyosarcoma or small-cell lung cancer. In window trials with ineffective or modestly active NMEs, we found no indication of a significant negative effect on overall survival for participating patients.

Conclusions: Provided close safety monitoring and careful patient selection, window trials are a safe option to investigate potential clinical activity of NMEs.