Cancer :: Alternative Phase II Trial Design Could Reduce Phase III Failures

An alternative design for phase II cancer clinical trials may improve success rates for new cancer drugs in phase III trials.

Phase II cancer trials are conducted in order to determine whether a new drug is effective enough to warrant further study.

Usually, this is demonstrated by treating all patients in the study with the new drug and showing that a certain proportion of these patients has a substantial reduction in the size of their tumors.

However, phase II tests are often not good predictors of a drug’s later success. Cancer drug development has been hindered by high rates of failure in phase III trials where the new drug is compared head-to-head with standard therapy to see whether it improves survival time or slows disease progression. To improve phase III success rates, it may be useful to consider alternative ways to evaluate drugs in phase II.

Theodore Karrison, Ph.D., of the University of Chicago and colleagues describe a phase II trial design that uses tumor size—measured on a continuous scale—as the measure of the drug’s success. In the study, two groups of patients receive different doses of the drug and a control group receives the standard therapy.

The authors argue that this design has the advantage of including a control group and making more efficient use of the data on tumor size changes. The design does require studying more patients, and its success at predicting phase III outcome has not been demonstrated. Nonetheless, the authors write, “With growing numbers of agents and agent classes available for evaluation, it is crucial to develop phase II clinical trial strategies that utilize patient resources efficiently and provide data more predictive of phase III results than current phase II approaches.”

In an accompanying editorial, Larry Rubinstein, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues discuss the potential problems with using tumor size as an endpoint, though they say it is worth further study. “If validated and used properly, this endpoint could provide an efficient early indication of potential benefit in situations in which neither objective tumor response nor progression-free survival is a feasible endpoint, and its use could facilitate randomized comparisons for subpopulations that are difficult to accrue,” the editorialists write.

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