Devita, Hellman, and Rosenberg's Cancer

LWBK1006-16 LWW-Govindan-Review December 12, 2011 18:55

Chapter 16•Design and Analysis of Clinical Trials 185

Question 16.8. Patients in a Phase II trial are often recruited in a two-stage manner that

allows a potential early stopping, thus saving patients from unnecessary

exposure to inactive agents. Which of the following is NOT true of a

two-stage design?

A. The optimal two-stage design minimizes the average sample size and

thus optimizes the protection of patients given an inactive agent.

B. Simon’s two-stage designs are often applied in Phase II trials on molec-

ularly targeted drugs and therapeutic cancer vaccines.

C. The minimax design minimizes the total sample size. Compared with

the optimal design, the minimax design usually enrolls more patients

in the first stage and fewer patients in total sample size.

D. With p0=0.10, p1=0.25, a type I error of 0.05, and 80% power,

for example, a Simon’s minimax design will enroll 22 patients in the

first stage. If three or more responses are observed, 18 more patients

will be enrolled in the second stage. If eight or more responses are

observed at the end of study, it will be concluded that the treatment

shows preliminary evidence of efficacy.

Question 16.9. Unlike cytotoxic agents that work by killing tumor cells, cytostatic agents

work via biologic effects that modify the environment of tumor growth;

that is, inhibition of a molecular target. Which of the following is NOT

true regarding early-phase trials on cytostatic agents such as molecularly

targeted drugs and cancer therapeutic vaccines?

A. Because cytostatic agents usually have a good safety profile, Phase I

trials on such drugs are often designed to identify a biologically active

dose rather than maximum tolerated dose.

B. Because therapeutic cancer vaccines work via stimulation of tumor-

reactive T cells, heavily treated patients with end-stage disease are

less likely to benefit from a cancer vaccine.

C. The response rate based on tumor shrinkage is the best primary end

point measuring treatment efficacy in Phase II trials on cytostatic

agents.

D. Because of the low toxicity profiles in cytostatic agents, factorial

designs and randomized studies have appealing features and are used

to evaluate multiple drugs in a single trial.

Question 16.10. Which of the following best describes Simon’s Phase 2.5 design on molec-

ularly targeted drugs and cancer therapeutic vaccines?

A. The design compares progression-free survival times of the same

patient from the current trial with his/her previous trial.

B. The design first treats all eligible patients with two to four courses of

the experimental drugs. Patients are then evaluated, and the experi-

mental drug is either continued or discontinued, depending on their

response to the initial treatment.

C. The design is similar to a Phase III trial except that it allows a relatively

large type I (false positive) error and targets for a relatively large

difference, thus requiring fewer patients.

D. The design will compare time to progression of patients in the study

with a prospectively identified and prognostically comparable histor-

ical control.