Tanespimycin in Treating Women With Refractory Locally Advanced or Metastatic Breast Cancer
Condition: Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: tanespimycin; laboratory biomarker analysis
Intervention description: Given IV; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well tanespimycin works in treating women with refractory
      locally advanced or metastatic breast cancer. Drugs used in chemotherapy, such as
      tanespimycin, work in different ways to stop tumor cells from dividing so they stop growing
      or die
    

Eligibility criteria:

        Inclusion Criteria:

          -  Primary adenocarcinoma of the breast confirmed by histology or cytology

          -  Locally advanced or metastatic disease not amenable to surgery or radiation therapy
             with curative intent

          -  At least 1 measurable (target) lesion (i.e. any malignant tumor mass that can be
             accurately measured in at least 1 dimension of >= 2 cm with conventional radiographic
             techniques or >= 1 cm with magnetic resonance imaging [MRI] or spiral computerized
             tomography [CT] scans), not previously irradiated

          -  Progressive disease following hormonal therapy in appropriate patients (ER-positive
             and/or indolent disease)

          -  Progressive disease following treatment with both an anthracycline and a taxane (as
             adjuvant therapy or for metastatic disease) or contraindication to such treatment

          -  All previous cytotoxic chemotherapy must have been discontinued at least 4 weeks
             before study entry and all acute toxicity of prior therapy (excluding alopecia and
             neurotoxicity) must be resolved to NCI CTC (Version 3.0) grade =< 1; patients must
             have discontinued treatment with nitrosoureas or mitomycin C at least 6 weeks prior to
             study entry

          -  All previous hormonal therapy must have been discontinued for at least 2 weeks before
             study entry

          -  Life expectancy of >= 3 months

          -  ECOG performance status (PS) of 0-2

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dL

          -  Creatinine (Cr) =< upper limit of normal (ULN) or Cr Clearance > 60 mL/min/m^2

          -  Total bilirubin =< 1.5X ULN

          -  Alanine aminotransferase (ALT) =< 1.5X ULN or =< 3X ULN with liver metastases

          -  Aspartate aminotransferase (AST) =< 5X ULN or =< 3X ULN with liver metastases

          -  Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women or
             women within 6 months of menopause

          -  Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other study procedures

          -  Evidence of a personally signed and dated informed consent document indicating that
             the patient (or a legally acceptable representative) has been informed and understands
             all pertinent aspects and the investigational nature of the trial

        Exclusion Criteria:

          -  Current treatment with any other anti-neoplastic agent, including trastuzumab;
             patients may continue to receive zoledronic acid for bone metastases or hypercalcemia

          -  Radiation therapy within 2 weeks of enrollment or surgery within 4 weeks

          -  Known brain or leptomeningeal metastatic disease requiring active therapy; (Patients
             with asymptomatic previously treated metastases to these areas are eligible)

          -  Any of the following conditions within 6 months of enrollment: myocardial infarction,
             severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident
             or transient ischemic attack, coronary/peripheral artery bypass grafting; patients who
             have experienced a pulmonary embolus, deep venous thrombosis or other clinically
             significant thromboembolic event within 6 months of enrollment are eligible if they
             are clinically stable on anticoagulation therapy

          -  Current active infection, including known human immunodeficiency virus (HIV)
             positivity; for HIV patients on highly active antiretroviral therapy (HAART), the
             pharmacokinetics of the investigation agent may be seriously affected; when
             appropriate, 17-AAG will be studied in patients with HIV on HAART

          -  Pregnancy or breastfeeding; because of the unknown effects on the developing
             fetus/newborn, patients who are pregnant or become pregnant should be excluded from
             protocol study; exclusion of breast feeding women would also be appropriate as it is
             not known whether 17-AAG may be excreted in breast milk and what effect this may have
             on a developing newborn; female patients must agree to use effective contraception
             during the study period, be surgically sterile, or be post-menopausal; in addition,
             male patients will be required to use effective contraception during the study period
             or be surgically sterile; the definition of effective contraception will be based on
             the judgment of the investigator

          -  Serious allergy to eggs (i.e. hypotension, dyspnea, anaphylaxis, edema)

          -  Treatment with any agents that interact with cytochrome P450 3A should be avoided and
             used with caution, if necessary; when possible, patients should be switched to
             alternative medications; patients requiring anticoagulation should not be treated with
             Coumadin and should be switched to a low molecular weight heparin injection; patients
             receiving treatment with a low molecular weight heparin will require episodic
             monitoring with the anti-factor Xa heparin assay

          -  Previous (within 5 years of enrollment) or current malignancies at other sites, except
             adequately treated basal cell or squamous cell skin cancers and carcinoma in situ of
             the cervix

          -  Other severe acute or chronic medical or psychiatric conditions or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration or may interfere with interpretation of study results and, in the
             judgment of the investigator, would make the patient inappropriate for study entry

          -  The use of concomitant medications that prolong or may prolong QTc are excluded

          -  Patients who have significant cardiac disease including heart failure that meets New
             York Heart Association (NYHA) class III and IV definitions, history of myocardial
             infarction within one year of study entry, uncontrolled dysrhythmias, or poorly
             controlled angina are excluded

          -  Patients who have a history of serious ventricular arrhythmia (VT or VF, >= 3 beats in
             a row), QTc >= 450 msec for men and 470 msec for women, or LVEF =< 40% by MUGA are
             excluded

          -  Patients with a prior history of cardiac or pulmonary toxicity after receiving
             anthracyclines such as doxorubicin, daunorubicin, mitoxantrone, bleomycin or BCNU

          -  Patients with greater or equal to grade 2 pulmonary or cardiac symptoms prior to study
             entry

          -  Patients with a history of prior radiation that potentially included the heart in the
             field (e.g., mantle)

          -  Patients with active ischemic heart disease within 12 months

          -  Patients with a history of uncontrolled dysrhythmias or requiring antiarrhythmic drugs

          -  Patients with congenital long QT syndrome; and patients with left bundle branch block

          -  Patients with symptomatic pulmonary disease requiring medication including the
             following: dyspnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, oxygen
             requirement and significant pulmonary disease, including chronic
             obstructive/restrictive pulmonary disease

          -  Patients that meet the Medicare criteria for home oxygen

          -  Patients with a prior history of chest radiation