A Phase I Study of Epothilone B Analog BMS 247550 in Combination With Carboplatin in Recurrent and/or Refractory Solid Tumors
I. Determine the maximum tolerated dose of BMS-247550 when given in combination with
carboplatin in patients with recurrent or refractory solid tumors.
II. Determine the dose-limiting toxicity and safety of this regimen in these patients.
III. Determine the plasma pharmacokinetics of this regimen in these patients. IV. Determine,
preliminarily, any antitumor activity of this regimen in these patients.
V. Correlate the protein expression of survivin with the expression of other apoptotic
regulators, the apoptotic index, and response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of BMS-247550.
Patients receive BMS-247550 IV over 1 hour on days 1, 8, and 15 followed by carboplatin IV
over 1 hour on day 1. Treatment repeats every 28 days for at least 2 courses in the absence
of disease progression or unacceptable toxicity. Patients with a complete response (CR)
receive 2 additional courses after achieving CR or up to a total of 6 courses. The first two
cohorts of 3-6 patients each receive escalating doses of BMS-247550 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which
at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).The third and
fourth cohorts of 10 patients each receive escalating doses of BMS-247550 until the MTD is
determined. The MTD is defined as the dose preceding that at which at least 3 of 10 patients
experience DLT. Once the MTD is determined for the third and fourth cohorts, 15 additional
patients are treated at the MTD. Patients are followed for 30 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of ixabepilone defined as the first dosage tier below the MAD in which =< 1/6 patients experiences a DLT
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|