The design and conduct of clinical trials in childhood brain tumors.

The orderly conduct of clinical research trials in pediatric oncology has laid the foundation for modern curative therapy in several childhood malignancies. Such types of large clinical trials are relatively new to pediatric neuro-oncology. New treatments such as single and combination chemotherapy agents are studied in a Phase II trial in children with specific recurrent primary brain tumors. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans and myelography allow the accurate determination of objective responses. The relative lack of promising Phase II trials has hampered the design of new Phase III studies for a variety of primary childhood brain tumors. The results of several Phase II trials may be incorporated into a prospective randomized Phase III study in which the endpoint is disease-free survival rather than response rate. Because of the rarity of specific types of primary childhood brain tumors, randomized Phase III trials are conducted more easily by cooperative cancer study groups. This article suggests some guidelines for the conduct of these Phase II and III trials in children with primary brain tumors so that accurate data may be accrued in an efficient manner.