Ixabepilone in Treating Patients With Locally Advanced or Metastatic Breast Cancer

Study Overview
=================
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.

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.

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

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: ixabepilone


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ixabepilone|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
male breast cancer, recurrent breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer