A Phase I Trial of Farnesyltransferase Inhibitor BMS-214662 (NSC 710086) Escalating to a 24 Hour Continuous Intravenous Infusion in Patients With Solid Tumors
I. To establish the maximum tolerated dose (MTD) and identify the dose limiting toxicities
(DLT) of the investigational agent BMS-214662 when escalated to a 24-hour continuous
intravenous infusion every 7 days for 3 consecutive weeks to patients with solid tumors who
have failed curative or survival prolonging therapy or for who no such therapies exist.
II. To establish and assess the safety of an appropriate dose for Phase II studies.
III. To characterize the pharmacokinetics of BMS-214662 in patients when escalated to a
24-hour continuous IV infusion.
IV. To assess the extent and duration of farnesyltransferase inhibition in peripheral blood
mononuclear cells and other relevant surrogate markers of pharmacological activity.
I. To describe any preliminary evidence of antitumor activity. II. To establish
pharmacodynamic relationships for the pharmacological effect of the drug upon surrogate
markers of activity and host toxicity.
III. To compare the toxicity profiles for the 1 hour IV infusion and 24 hr continuous IV
infusion administration schedules, assuming that the 24 hr infusion schedule is feasible.
OUTLINE: This is a dose-prolongation, dose-escalation study.
Single patient cohorts receive BMS-214662 IV over escalating periods of 2, 4, 8, 16, and 24
hours weekly for 3 weeks followed by 1 week of rest. If no patient experiences dose-limiting
toxicity (DLT), dose escalation proceeds in the single patient cohorts.
Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression
or unacceptable toxicity. Individual patient cohorts may increase their duration of
BMS-214662 infusion in subsequent courses to the current duration safely reached.
Beginning with the infusion level at which DLT is first encountered by a single patient,
cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience DLT. An additional cohort of 10 patients is treated at the MTD.
Patients are followed for at least 4 weeks.
PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of BMS-214662, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Up to 28 days
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|