BMS-247550: Treating Patients With Advanced Solid Tumors, Breast Cancer or Recurrent Ovarian Cancer

Sponsor

Albert Einstein College of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT00005807

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Actual Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of BMS-247550 in treating patients who have metastatic, recurrent, or locally advanced, ovarian cancer, breast cancer, or metastatic or unresectable solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Ovarian Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: BMS-247550	Phase 1

Detailed Description

OBJECTIVES:

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 regimen.
Determine any evidence of antitumor activity of this treatment regimen in these patients.
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 regimen.
Investigate Multi-Drug Resistance Gene (MDR1), Multidrug Resistance-associated Protein (MRP) Gene, and canalicular multispecific organic anion transporter 1(cMOAT) messenger ribonucleic acid (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 toxicity.

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 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Scientific Exploratory Study of Epothilone B Analog in Patients With Solid Tumors and Gynecological Malignancies

Actual Study Start Date :

Jul 1, 2000

Actual Primary Completion Date :

Aug 1, 2004

Actual Study Completion Date :

Aug 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treated Participants dose escalation treatment	Drug: BMS-247550 anticancer agent for the treatment of patients with malignant tumors. Other Names: epothilone derivative

Arm

Intervention/Treatment

Experimental: Treated Participants

dose escalation treatment

Drug: BMS-247550

anticancer agent for the treatment of patients with malignant tumors.

Other Names:

epothilone derivative

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed metastatic or unresectable solid malignancy for which no standard or curative therapies exist or are no longer effective
Metastatic, recurrent, or locally advanced breast, ovarian, or other cancer
Hemoglobin at least 9.0 g/dL
WBC at least 3,000/mm3
Absolute neutrophil count at least 1,500/mm3
Platelet count at least 100,000/mm3
Bilirubin normal
AST/ALT no greater than 3 times upper limit of normal
Gilbert's syndrome allowed
Creatinine no greater than 2 mg/dL

Exclusion Criteria:

symptomatic congestive heart failure
unstable angina pectoris
cardiac arrhythmia
grade 2 or greater clinical neuropathy
prior allergy or hypersensitivity reaction (grade 2 or greater) to prior paclitaxel or other therapy containing Cremophor EL
allergy or intolerance to steroids, diphenhydramine, cimetidine, or ranitidine
uncontrolled concurrent illness
active infection
pregnant or nursing
other concurrent anticancer therapies or commercial agents
other concurrent investigational agents
other concurrent highly active antiretroviral therapy for HIV-positive patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Einstein Clinical Cancer Center	Bronx	New York	United States	10461
2	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016