Phase II

If the sponsor judges the Phase I drug to be safe and promising, the next step is a Phase II trial to further investigate safety and efficacy.   The Phase II trial may then proceed with the presumed safest dose calculated by one-half the MTD that was determined on the Phase I trial.  On average, 70% of phase I drugs go on to phase II.  Since oncology drugs such as chemotherapy often have more toxic side effects then general medicine drugs, the effective chemotherapy dose may sometimes be just below the MTD with multiple grade 2-3 toxic side effects tolerated for the anticipated effect of tumor response.

Phase II trials typically involve 20-40 patients at 2-6 clinic sites.  These trials further determine safety, but also focus on efficacy.  Hence, Phase II trials often “make or break” the future of an experimental agent.  On average, only 33% of Phase II drugs go on to Phase III.  A common phase II protocol design investigates effects of study drug combinations with already approved standard drugs.   The trial may test study drug versus study drug plus standard drug to discover if additive (2+2=4) or synergistic (2+2=5) tumor effects occur.  A randomized crossover design of a phase II trials is attractive because if patients on one study arm progress, then they may crossover to another study arm while staying on study, therefore maximizing their exposure to both combinations of drug.  Since phase I and II trials of experimental drugs enroll a small limited number of patients, they may have waiting lists and only be open for a short time.