Paclitaxel, Nab-paclitaxel, or Ixabepilone With or Without Bevacizumab in Treating Patients With Stage IIIC or Stage IV Breast Cancer
Condition: Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IIIC Breast Cancer AJCC v6; Stage IV Breast Cancer AJCC v6 and v7
MeSH terms: Breast Neoplasms
Intervention: Bevacizumab; Ixabepilone; Laboratory Biomarker Analysis; Nab-paclitaxel; Paclitaxel; Questionnaire Administration
Intervention description: Given IV; Given IV; Correlative studies; Given IV; Given IV; Ancillary studies
Intervention MeSH terms: Paclitaxel; Epothilones; Epothilone B; Albumin-Bound Paclitaxel; Bevacizumab; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 799.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies the side effects and how well different chemotherapy
      regimens with or without bevacizumab work in treating patients with stage IIIC or stage IV
      breast cancer. Drugs used in chemotherapy, such as paclitaxel, paclitaxel albumin-stabilized
      nanoparticle formulation (nab-paclitaxel), and ixabepilone, work in different ways to stop
      the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Bevacizumab may block tumor growth by targeting certain cells
      and slowing the growth of blood vessels to the tumor. It is not yet known which treatment
      regimen is more effective in treating patients with breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic confirmation of invasive cancer of the breast

          -  Stage IV disease or stage IIIC disease (using American Joint Committee on Cancer
             [AJCC] criteria, 6th edition) not amenable to local therapy

          -  Patients may not have a "currently active" second malignancy other than non-melanoma
             skin cancers; patients are not considered to have a "currently active" malignancy if
             they have completed therapy and are considered by their physician to be at less than
             30% risk of relapse

          -  Patients with human epidermal growth factor receptor 2 (HER2) negative disease are
             eligible; patients with HER2+ disease are eligible providing they have previously
             received trastuzumab or lapatinib; documentation of progression on HER2 directed
             therapy is not required; Her2/neu status must be known at the time of protocol
             registration

          -  Estrogen receptor (ER) and progesterone receptor (PgR) status must be known at the
             time of registration; ER and/or PgR >= 1% cells will be considered positive

          -  Prior treatment may include adjuvant or neoadjuvant taxane, however, the interval
             between completion of adjuvant or neoadjuvant therapy and disease recurrence must be
             >= 12 months

          -  No prior chemotherapy for metastatic breast cancer

          -  Any number of prior hormonal therapies are allowed; the last dose should have been
             administered at least 7 days prior to the initiation of protocol therapy

          -  Prior radiotherapy must be completed at least 2 weeks prior to study entry

          -  Treatment with bisphosphonates is allowed and recommended as per American Society of
             Clinical Oncology (ASCO) guidelines

          -  Prior trastuzumab or lapatinib required for patients with HER2 overexpressing tumors

          -  Prior treatment with bevacizumab is allowed

          -  Patients must not have had a major surgical procedure, open biopsy, or significant
             traumatic injury within 28 days prior to study registration, and must have fully
             recovered from any such procedure

               -  The following are not considered to be major procedures: thoracentesis,
                  paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic
                  ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies
                  and routine dental procedures

          -  Patients must not have anticipation of need for a major surgical procedure during the
             course of the study

          -  There are no restrictions on core biopsies, placement of a vascular access device or
             other minor procedures prior to registration

               -  Placement of a vascular access device after starting study therapy should be
                  performed between day 15 and 28 of a treatment cycle (but not less than 48 hours
                  before the next dose of bevacizumab) to allow for sufficient healing

          -  Patients must have measurable disease (target lesions): measurable disease is defined
             as at least one lesion that can be accurately measured in at least one dimension
             (longest diameter to be recorded) as >= 2.0 cm with conventional techniques or as >= 1
             cm with spiral computed tomography (CT) scan

               -  Lesions that are considered non-measurable include the following:

                    -  Bone lesions

                    -  Leptomeningeal disease

                    -  Ascites

                    -  Pleural/pericardial effusion

                    -  Inflammatory breast disease

                    -  Lymphangitis cutis/pulmonitis

                    -  Abdominal masses that are not confirmed and followed by imaging techniques

                    -  Cystic lesions

          -  Patients with pre-existing peripheral neuropathy >= grade 2 are not eligible for this
             study

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance
             status of =< 1 to be eligible for this trial

          -  Women must not be pregnant or breast feeding; premenopausal women must have a negative
             serum or urine beta-human chorionic gonadotropin (Hcg)

          -  Patients with a history of Common Terminology Criteria for Adverse Events (CTCAE)
             grade >= 3 hypersensitivity to paclitaxel or Cremophor® EL are not eligible

          -  Patients with a history of abdominal fistula, or intra-abdominal abscess within 6
             months prior to study registration are not eligible

          -  Patients with a history of gastrointestinal (GI) perforation within 12 months prior to
             registration are not eligible

          -  Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or
             lower GI bleeding) within 6 months prior to registration are not eligible

          -  Patients must not have a history of clinically significant cardiovascular disease that
             includes the following:

               -  Uncontrolled hypertension defined as systolic blood pressure > 150 and/or
                  diastolic blood pressure > 90 mmHg on antihypertensive medications or any prior
                  history of hypertensive crisis or hypertensive encephalopathy

               -  History of myocardial infarction or unstable angina within past 6 months

               -  New York Heart Association (NYHA) congestive heart failure grade 2 or greater

               -  Symptomatic peripheral vascular disease

               -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or
                  arterial thrombotic events

          -  Patients on full dose anticoagulants must be on a stable dose of warfarin, or be on a
             stable dose of low molecular weight (LMW) heparin; patients receiving anti-platelet or
             on daily prophylactic dose aspirin are eligible, as are patients receiving stable
             doses of anticoagulation for atrial fibrillation

          -  Patients may not have a history of stroke or transient ischemic attack within 6 months
             prior to study registration

          -  Patients with a history of seizures must be well controlled with standard medication

          -  Patients must not have progressing or untreated central nervous system (CNS)
             metastases or leptomeningeal disease; patients with a history of resected brain
             metastases with stable magnetic resonance imaging (MRI) scans for 3 months including
             within 4 weeks of study start are eligible; patients with a history of gamma knife
             radiosurgery or whole brain radiation with stable MRI scans for 3 months including
             within 4 weeks of study start are eligible

          -  No serious, non-healing wound, ulcer or bone fracture

          -  Life expectancy of >= 12 weeks

          -  Granulocytes >= 1,500/ul

          -  Platelet count >= 100,000/ul

          -  Creatinine =< 2.0 mg/dL

          -  Bilirubin < 1.5 mg/dL (unless due to Gilbert's syndrome)

          -  Transaminases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) =<
             2.5 x upper limit of normal (ULN)

          -  Serum or urine beta-Hcg negative in premenopausal women of child-bearing potential

          -  Urine protein =< 1+ protein* or urine protein: creatinine ratio (UPC) < 1

               -  Patients discovered to have >= 2+ proteinuria at baseline must undergo a 24-hour
                  urine collection that must demonstrate < 1 g of protein/24 hr or UPC ratio =< 1
                  to allow participation in the study