Ixabepilone in Treating Patients With Locally Advanced or Metastatic Breast Cancer

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.

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.

Eligibility Criteria:
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