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

Sponsors and Collaborators:	Albert Einstein College of Medicine of Yeshiva University National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00005807

Purpose

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	Intervention	Phase
Breast Cancer Ovarian Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: ixabepilone	Phase I

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Ovarian Cancer

Drug Information available for: Ixabepilone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	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

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

July 2000

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005807

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 of Yeshiva University

National Cancer Institute (NCI)

Investigators

Study Chair:

Franco M. Muggia, MD

New York University School of Medicine

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Study ID Numbers:	CDR0000067800, AECM-9911378, NCI-98, NYU-0006
Study First Received:	June 2, 2000
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00005807 History of Changes
Health Authority:	United States: Federal Government

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

Study placed in the following topic categories:

Epothilone B
Ovarian Neoplasms
Skin Diseases
Gonadal Disorders
Epothilones
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Urogenital Neoplasms
Breast Cancer, Male
Ovarian Diseases

Ovarian Epithelial Cancer
Recurrence
Genital Diseases, Female
Soft Tissue Sarcomas
Malignant Mesenchymal Tumor
Breast Neoplasms, Male
Sarcoma
Ovarian Cancer
Endocrinopathy
Breast Diseases
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Ovarian Neoplasms
Skin Diseases
Gonadal Disorders
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Urogenital Neoplasms

Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Neoplasms
Neoplasms by Site
Breast Diseases
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009