Epothilone B in Treating Patients With CNS Metastases From Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as epothilone B, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well epothilone B works in treating patients with CNS metastases from breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the 3-month CNS-progression free survival of patients with CNS metastases secondary to breast cancer treated with epothilone B. Secondary Determine the toxicity of this drug in these patients. Determine the CNS response rate and duration of CNS response in patients treated with this drug. Determine the systemic disease response rate and duration of systemic response in patients treated with this drug. Determine the overall survival of patients treated with this drug. OUTLINE: This is a multicenter, open-label study. Patients receive epothilone B IV over 20 minutes on day 1. Courses repeat every 21 days in the absence of disease progression, satisfactory response, or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Official Title
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Phase II Trial of Patupilone in Patients With Brain Metastases From Breast Cancer

Conditions
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Breast Cancer, Metastatic Cancer

Intervention / Treatment
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* Biological: epothilone B


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed carcinoma of the breast CNS metastases (i.e., brain parenchymal lesions and/or leptomeningeal disease), meeting 1 of the following criteria: Recurrent or progressive CNS metastases after whole brain radiotherapy If only evaluable site of CNS progression has been previously treated with stereotactic radiosurgery, radiation necrosis must be excluded by radiographic (e.g., positron emission tomography scan or magnetic resonance spectroscopy) or histologic assessment Newly diagnosed, untreated, asymptomatic brain or leptomeningeal metastases Patient must be neurologically stable, as demonstrated by a stable dose of steroids and anticonvulsants for ≥ 1 week prior to obtaining baseline gadolinium-enhanced MRI of the brain and/or ≥ 1 week prior to beginning study treatment No CNS complications requiring urgent neurosurgical intervention (e.g., resection or shunt placement) Hormone receptor status not specified PATIENT CHARACTERISTICS: Male or female Menopausal status not specified Karnofsky performance status 60-100% Life expectancy ≥ 3 months Absolute neutrophil count > 1,500/mm^3 Hemoglobin > 9.0 g/dL Platelet count > 100,000/mm^3 (red blood cell transfusion and repeat evaluation allowed) Bilirubin < 1.5 times upper limit of normal (ULN) AST and ALT < 2.5 times ULN Alkaline phosphatase < 2.5 times ULN Creatinine < 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study therapy No known hypersensitivity to epothilones No peripheral neuropathy > grade 1 No unresolved diarrhea within the past 7 days Grade 0 diarrhea required at study entry No concurrent serious medical illness (e.g., HIV positivity or active hepatitis B or C) No severe cardiac insufficiency (e.g., New York Heart Association class III-IV heart disease) with uncontrolled and/or unstable cardiac or coronary artery disease No active or suspected acute or chronic uncontrolled infection, including abscess or fistulae No other malignancy within the past 3 years except curatively treated nonmelanoma skin cancer, prostate cancer, or carcinoma in situ of the cervix No history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits No contraindications to MRI, including any of the following: Pacemaker Ferromagnetic implants Claustrophobia Extreme obesity PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 2 weeks since prior noncytotoxic drugs (e.g., small molecule-targeted drugs) and recovered More than 3 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered More than 3 weeks since prior intracranial surgery and recovered More than 4 weeks since prior radiotherapy and recovered More than 4 weeks since prior major surgery More than 28 days since prior investigational compounds or drugs No prior epothilones No concurrent known diarrheagenic agents No other concurrent anticancer agents, including investigational agents, biological agents, or chemotherapy No other concurrent experimental therapies Concurrent hormone therapy and/or trastuzumab (Herceptin®) allowed No concurrent Coumadin® or other agents containing warfarin Low dose Coumadin® (≤ 1 mg) for prophylactic maintenance of indwelling lines or ports allowed No concurrent radiotherapy for central metastases (e.g., vertebral or mediastinal metastases) Concurrent radiotherapy for local peripheral metastases not being used as marker lesions allowed No concurrent prophylactic hematopoietic growth factors during course 1 No concurrent herbal or nontraditional medications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epothilone B<br> | Biological: epothilone B<br>* Patupilone will be administered as a single intravenous infusion over 20 minutes, once every 3 weeks. Patupilone will be administered at a dose of 10 mg/m2 (q3weeks) with actual body weight.<br>* Other names: Patupilone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central Nervous System (CNS) Progression-free Survival(PFS) | The number of patients that are documented to have progression free survival at 3 months after treatment. Progression free is define as <25% increase in tumor area. PFS will be measured from the date of entry into the trial to the date of documented progression of brain metastases or death. | 3 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as Measured by NCI CTCAE v3.0 | Percent of patients that experience the most common grade 3 and above toxicities possibly related to study drug - to be measured using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0. | 3 months after treatment | 
| CNS Response Rate, for Measurable Disease Will be Assessed by the Modified McDonald Criteria | Complete Response (CR): the circumstance when the tumor is no longer seen by neuroimaging Partial Response (PR): Decrease of >50% in the product of two diameters Stable Disease (SD): the circumstance when the scan shows no change. Progression (P): a > 25% increase in tumor area (two diameters) | 3 months after treatment | 
| Systemic Disease Response Rate for Measurable Disease Will be Assessed by the Modified McDonald Criteria | Complete Response (CR): the circumstance when the tumor is no longer seen by neuroimaging Partial Response (PR): Decrease of >50% in the product of two diameters Stable Disease (SD): the circumstance when the scan shows no change. Progression (P): a > 25% increase in tumor area (two diameters) | 3 months after treatment | 
| Overall Survival | Median time (months) that patients survived during the duration of the study. | 48 months from start of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer, tumors metastatic to brain, leptomeningeal metastases, male breast cancer