Trial Information

Phase I Study of R031-7453, a Novell Cell Cycle Inhibitor, Administered as Escalating Oral Doses in Adults With Solid Tumors: 4-Day Schedule

OBJECTIVES: I. Determine the maximum tolerated dose of Ro 31-7453 in patients with solid
tumors. II. Determine the toxicity of Ro 31-7453 in this patient population. III. Evaluate
the pharmacokinetics and major metabolites of Ro 31-7453 in these patients. IV. Assess any
antitumor activity of Ro 31-7453 in these patients.

OUTLINE: This is a dose escalation study. Patients are treated on one of two treatment arms.
In the first stage, cohorts of 1 patient each on arm I receive oral Ro 31-7453 twice daily
on days 1-4, and cohorts of 1 patient each on arm II receive oral Ro 31-7453 once daily on
days 1-4 at two dose levels higher than for arm I. Dose escalation ceases for each arm with
the first instance of dose limiting toxicity (DLT). Two additional patients are entered at
the stopping dose for each arm. If no further DLT occurs, the study proceeds to the second
stage. In the second stage, dose escalation continues in increments of one dose level for
each dosing schedule (arms I and II). Cohorts of 3-6 patients receive escalating doses of Ro
31-7453 in the absence of DLT. If 2 of 6 patients experience DLT at a dose level, escalation
ceases and the maximum tolerated dose is defined as the previous dose level. Treatment
continues every 3 weeks for 8 courses in the absence of disease progression or unacceptable
toxicity. After completion of the 8 courses, patients may continue treatment until disease
progression at the discretion of the investigator and the study sponsor. Patients are
followed at 4 weeks.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study over 18 months.