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

Study Description

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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: ixabepilone	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 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 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

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Study Type :	Interventional (Clinical Trial)
Primary Purpose:	Treatment
Official Title:	A Phase I Scientific Exploratory Study of Epothilone B Analog (BMS-247550; NSC #710428) in Patients With Solid Tumors and Gynecological Malignancies
Study Start Date :	July 2000

Arms and Interventions

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Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Part I:

  • Histologically or cytologically confirmed metastatic or unresectable solid malignancy for which no standard or curative therapies exist or are no longer effective

• Part II:

  • Metastatic, recurrent, or locally advanced breast, ovarian, or other cancer

    • At least 1 site amenable to biopsy
  • No known brain metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Male or female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-1 OR
• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• 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

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 3 times upper limit of normal
• Gilbert's syndrome allowed

Renal:

• Creatinine no greater than 2 mg/dL

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• No grade 2 or greater clinical neuropathy
• No prior allergy or hypersensitivity reaction (grade 2 or greater) to prior paclitaxel or other therapy containing Cremophor EL
• No allergy or intolerance to steroids, diphenhydramine, cimetidine, or ranitidine
• No other uncontrolled concurrent illness
• No active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 weeks since prior radiotherapy
• No prior radiotherapy to more than 35% of bone marrow
• Prior whole pelvic radiotherapy allowed

Surgery:

• See Disease Characteristics

Other:

• No other concurrent anticancer therapies or commercial agents
• No other concurrent investigational agents
• No concurrent highly active antiretroviral therapy for HIV-positive patients

Contacts and Locations

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Locations

United States, New York
Albert Einstein Clinical Cancer Center
Bronx, New York, United States, 10461
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016

Sponsors and Collaborators

Albert Einstein College of Medicine, Inc.

National Cancer Institute (NCI)

Investigators

Study Chair:	Franco M. Muggia, MD	New York University School of Medicine

More Information

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Publications of Results:

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.

ClinicalTrials.gov Identifier:	NCT00005807 History of Changes
Other Study ID Numbers:	CDR0000067800; AECM-9911378; NCI-98; NYU-0006
First Posted:	January 27, 2003
Last Update Posted:	July 24, 2008
Last Verified:	September 2003

Keywords provided by National Cancer Institute (NCI):

stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer; unspecified adult solid tumor, protocol specific	ovarian stromal cancer; stage III ovarian germ cell tumor; stage IV ovarian germ cell tumor; recurrent ovarian germ cell tumor; borderline ovarian surface epithelial-stromal tumor; ovarian sarcoma; male breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Ovarian Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Endocrine Gland Neoplasms	Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders