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

NCT ID: NCT00005807

Last Updated: 2018-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-07-31
• Study Completion Date: 2004-08-31

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.

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.

Conditions

Breast Cancer; Ovarian Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treated Participants

dose escalation treatment

Group Type: EXPERIMENTAL

BMS-247550

Intervention Type: DRUG

anticancer agent for the treatment of patients with malignant tumors.

Interventions

BMS-247550

anticancer agent for the treatment of patients with malignant tumors.

Intervention Type: DRUG

Other Intervention Names

epothilone derivative

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Albert Einstein College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Franco M. Muggia, MD

Role: STUDY_CHAIR

NYU Langone Health

Sridhar Mani, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein College of Medicine

Locations

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Albert Einstein Clinical Cancer Center

The Bronx, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 12114401 (View on PubMed)

Other Identifiers

AECM-9911378

Identifier Type: -

Identifier Source: secondary_id

NCI-98

Identifier Type: -

Identifier Source: secondary_id

NYU-0006

Identifier Type: -

Identifier Source: secondary_id

CDR0000067800

Identifier Type: -

Identifier Source: org_study_id