Ixabepilone in Treating Patients With Locally Advanced or Metastatic Breast Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00045097

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

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

PURPOSE: This phase II trial is studying how well ixabepilone works in treating patients with locally advanced or metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: ixabepilone	Phase 2

Detailed Description

OBJECTIVES:

Determine any antitumor activity of ixabepilone, in terms of objective response rate, in patients with incurable, locally advanced or metastatic breast cancer.
Determine the toxicity of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior taxane therapy (yes vs no).

Patients (with or without prior taxane exposure) receive ixabepilone IV over 1 hour on days 1-5. An additional cohort of 37 patients who have received prior taxane therapy are then accrued to receive ixabepilone IV over 1 hour on days 1-3 at a higher starting dose. For all patients, courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who receive more than 6 courses with satisfactory response may be treated every 4-5 weeks.

Patients removed for unacceptable toxicty are followed periodically.

PROJECTED ACCRUAL: A total of 105 patients (at least 74 with and 21 without prior taxane exposure) will be accrued for this study within 26 months.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Clinical Trial Of BMS-247550 (NSC 710428), An Epothilone B Analog, In Patients With Breast Carcinoma

Study Start Date :

May 1, 2002

Actual Study Completion Date :

Jul 1, 2007

Outcome Measures

Primary Outcome Measures

Anti-tumor activity as measured by CT scans and bone scans at baseline and every other course []
Ixabepilone toxicity as measured by lab studies at baseline and after every course []

Secondary Outcome Measures

Tumor tubulin polymerization and p53 expression from biopsy specimens and cDNA microarray testing at baseline and prior to course 2. []
Neurotoxicity assessment as measured by Semmes-Weinstein monofilament, sharpened Rombrog, one-legged stance, Jebsen Test of hand function, the grooved pef board , and subjective questionnaires at baseline and prior to every other course []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed* adenocarcinoma of the breast
Incurable, locally advanced or metastatic disease
Primarily stage IV disease, but some inoperable stage III disease may be eligible (e.g., a patient with T4 and/or N2-3 disease who cannot receive doxorubicin or who has already received other therapy) NOTE: *Patients with no available tissue for histologic confirmation but who have documentation of breast surgery and prior chemotherapy are eligible upon approval of the principal investigator
Measurable disease
No evidence of CNS metastases by brain MRI or contrast head CT scan
CNS metastases controlled by radiotherapy or surgical resection at least 6 months prior to study enrollment are allowed
Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Female or male

Menopausal status

Not specified

Performance status

ECOG 0-2

Life expectancy

At least 3 months

Hematopoietic

Granulocyte count at least 1,200/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN) (3 times ULN if there is clinical evidence of Gilbert's disease)
AST and ALT no greater than 2.5 times ULN

Renal

Creatinine normal OR
Creatinine clearance greater than 40 mL/min

Other

No poor medical risk due to other nonmalignant systemic disease
No active uncontrolled infection
No sensory, motor, or cranial neuropathy or neuropathic pain grade 2 or greater (unless neuropathy is clearly due to underlying breast cancer)
No other concurrent serious medical illness
No prior severe hypersensitivity reactions to agents containing Cremophor EL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

More than 4 weeks since prior filgrastim (G-CSF), pegfilgrastim, or thrombopoietin (or other platelet growth factors)
No concurrent immunotherapy

Chemotherapy

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
No other concurrent chemotherapy for breast cancer

Endocrine therapy

More than 2 weeks since prior hormonal therapy
No concurrent hormonal therapy

Radiotherapy

See Disease Characteristics
No prior craniospinal radiation
No prior total body irradiation
More than 4 weeks since prior radiotherapy

Surgery

See Disease Characteristics

Other

No other concurrent investigational drugs
No concurrent cytochrome p450 3A4 inhibitors, including any of the following:
Clarithromycin
Erythromycin
Troleandomycin
Delaviridine
Nelfinavir
Amprenavir
Ritonavir
Indinavir
Saquinavir
Lopinavir
Itraconazole
Ketoconazole
Fluconazole (> 200 mg/day)
Voriconazole
Nefazodone
Fluvoxamine
Verapamil
Diltiazem
Amiodarone
Concurrent bisphosphonates for bone metastases allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Suburban Hospital	Bethesda	Maryland	United States	20814
2	Oncology Care Associates	Bethesda	Maryland	United States	20817
3	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
4	NCI - Center for Cancer Research	Bethesda	Maryland	United States	20892