Phase II studies are designed to assess potential efficacy and activity of the proposed gene therapy strategies in a larger patient population. These trials often evaluate the effectiveness and dose ranging of the new agent for a specific disease and patient population. Traditional endpoints of phase II trials with conventional agents often utilize tumor response (i.e., partial or complete response but many of the biologic agents may be cytostatic therapies that do not cause tumor shrinkage but still lead to antiangiogenic or immunomodulatory effects). Assessment of the true activity of these agents may therefore not be possible with these classic endpoints. Alternative endpoints such as time to progression, stable disease, or symptom improvement may therefore need to be considered (32). Other potential endpoints may include decreases in tumor markers such as prostate-specific antigen (PSA) or CEA (33). It is also critical to recognize that biologic agents may impact only a small subset of patients and studies may need to be designed to stratify patients according to biologic parameters. These correlative studies may be critical in identifying therapeutic subsets of patients. New federal regulations may impede this process by imposing strict criteria on the collection of tissue from patients and children with patients often choose not to participate in these critical steps (34). The design of these trials should therefore take into account the need for biopsies to be limited in number to encourage active patient participation because the collection of tissue may allow future biologic information to be incorporated in sensitivity analyses that would not be possible if tissue collection had not occurred.
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