A Phase I Scientific Exploratory Study of Epothilone B Analog (BMS-247550; NSC #710428) in Patients With Solid Tumors and Gynecological Malignancies
- Determine the maximum tolerated dose, recommended phase II dose, and associated toxic
effects of BMS-247550 in patients with advanced solid tumors.
- Determine the pharmacokinetic and pharmacodynamic relationship of this treatment
regimen in these patients.
- Assess the extent of microtubule bundle and mitotic aster formation and cell cycle
kinetics in peripheral blood mononuclear cells in these patients treated with this
- Determine any evidence of antitumor activity of this treatment regimen in these
- Evaluate the relationship between tumor response and the occurrence of mutation in the
class 1 isotype of B-tubulin and B-tubulin isotype distribution in patients with
advanced or recurrent solid tumors, ovarian cancer, or breast cancer treated with this
- Investigate MDR1, MRP, and cMOAT mRNA and protein expression as prognosticators of
tumor response in these patients treated with this regimen.
- Determine the relationship between stathmin expression and phosphorylation status as a
function of response in these patients treated with this regimen.
- Correlate the expression of proapoptotic (p53, bax, bad, and bid) and antiapoptotic
(survivin, inhibitors of apoptotic proteins, bcl-2, and bcl-x) proteins in tumor
samples and/or ascites with response and clinical outcome in these patients treated
with this regimen.
OUTLINE: This is a dose-escalation, multicenter study.
- Part I: Patients with advanced solid tumors receive BMS-247550 IV over 1 hour every 3
weeks. Treatment continues in the absence of disease progression or unacceptable
Cohorts of 3-6 patients 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 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
- Part II: Patients with ovarian, breast, or other cancer receive BMS-247550 as in the
part I portion of the study at the MTD. Treatment continues in the absence of disease
progression or unacceptable toxicity.
Patients are followed at 2 months.
PROJECTED ACCRUAL: Approximately 42-66 patients will be accrued for this study within 12-16
Primary Purpose: Treatment
Franco M. Muggia, MD
New York University School of Medicine
United States: Federal Government
|NYU School of Medicine's Kaplan Comprehensive Cancer Center||New York, New York 10016|
|Albert Einstein Clinical Cancer Center||Bronx, New York 10461|