Treating Patients With Advanced Solid Tumors, Breast Cancer or Recurrent Ovarian Cancer

Breast Cancer Clinical Trial

— BMS-247550  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005807
• Other study ID #: CDR0000067800
• Secondary ID: AECM-9911378NCI-
• Status: Completed
• Phase: Phase 1
• Start date: July 2000
• Est. completion date: August 2004

Study information

• Verified date: October 2018
• Source: Albert Einstein College of Medicine, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 2004
• Est. primary completion date: August 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• BMS-247550
anticancer agent for the treatment of patients with malignant tumors.

Locations

Country	Name	City	State
United States	Albert Einstein Clinical Cancer Center	Bronx	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine, Inc.	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

McDaid HM, Mani S, Shen HJ, Muggia F, Sonnichsen D, Horwitz SB. Validation of the pharmacodynamics of BMS-247550, an analogue of epothilone B, during a phase I clinical study. Clin Cancer Res. 2002 Jul;8(7):2035-43. — View Citation