Epothilone B in Treating Patients With CNS Metastases From Breast Cancer
Condition: Breast Cancer; Metastatic Cancer
MeSH terms: Breast Neoplasms; Neoplasm Metastasis
Intervention: epothilone B
Intervention description: 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.
Intervention MeSH terms: Epothilones; Epothilone B
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent breast cancer; stage IV breast cancer; tumors metastatic to brain; leptomeningeal metastases; male breast cancer

Summary:

      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.
    

Eligibility criteria:

        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