Clinical trial NCT00370552 (phase 2, status: completed)
Conditions: metastatic breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: ixabepilone, 16 mg/m^2 + bevacizumab, 10 mg/kg, ixabepilone, 40 mg/m^2 + bevacizumab, 15 mg/kg, paclitaxel, 90 mg/m^2 + bevacizumab, 10 mg/kg
SMILES: [H][C@]12C[C@H](NC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@]1(C)O2)C(\C)=C\C1=CSC(C)=N1, [H][C@]12C[C@H](NC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@]1(C)O2)C(\C)=C\C1=CSC(C)=N1, [H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C
Eligibility criteria:

        Inclusion criteria:

          -  Locally recurrent or metastatic breast cancer, previously untreated with chemotherapy
             for advanced disease.

          -  At least 1 target lesion per RECIST criteria. Locally recurrent disease must not be
             amenable to resection with curative intent.

          -  No previous cytotoxic chemotherapy for locally recurrent/metastatic disease.

          -  Relapse 12 months or more after completing prior adjuvant or neoadjuvant taxane
             therapy.

          -  No previous breast cancer known to overexpress or amplify the human epidermal growth
             factor receptor 2 gene.

          -  Prior hormonal therapy in adjuvant, recurrent, or metastatic setting allowed but must
             have been discontinued at least 2 weeks before randomization.

          -  Karnofsky performance status of 80 to 100 or Eastern Cooperative Oncology Group
             performance status of 0 to 1.

          -  Estimated life expectancy of at least 12 weeks.

          -  Recovery from recent therapy (except for alopecia), including chemotherapy,
             immunotherapy, biologic therapy, or investigational product. Any such therapy must
             have been completed at least 3 weeks before randomization and at least 6 weeks from
             use of nitrosourea, or mitomycin.

          -  Recovery from recent surgery and radiation therapy. At least 1 week since minor
             surgery and/or focal/palliative radiation therapy; at least 3 weeks from radiation; at
             least 4 weeks from major surgery; and at least 8 weeks from liver resection,
             thoracotomy, or neurosurgery.

          -  Absolute neutrophil count ≥1500/mm^3.

          -  Hemoglobin ≥9 g/dL.

          -  Platelets ≥100,000/mm^3.

          -  Total bilirubin ≤1.5 times the upper limit of normal (ULN).

          -  Aspartate aminotransferase or alanine aminotransferase ≤2.5*ULN.

          -  Normal partial thromboplastin time and either international normalized ratio or
             prothrombin time <1.5*ULN.

          -  Serum creatinine ≤1.5*ULN or 24-hour creatinine clearance >60 mL/min.

          -  Urine dipstick for proteinuria <2+ (negative, trace, or +1). Participants with ≥2+
             proteinuria at baseline were to undergo 24-hour urine collection and demonstrate ≤1g
             of protein in 24 hours to be eligible.

        Exclusion criteria:

          -  Women of child-bearing potential (WOCBP) unwilling or unable to use an acceptable
             method of birth control to avoid pregnancy for the entire study period and up to 6
             months after treatment with bevacizumab.

          -  Women who were pregnant or breastfeeding.

          -  Women with a positive pregnancy test on enrollment or prior to study drug
             administration.

          -  Sexually active fertile men, whose partners were WOCBP, not using an adequate method
             of birth control.

          -  Evidence of baseline sensory or motor neuropathy.

          -  Serious infection or nonmalignant medical illnesses uncontrolled or the control of
             which could be jeopardized by this therapy.

          -  History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess,
             serious gastric ulcer, or bone fracture within 6 months of study entry.

          -  History of hypertensive crisis or hypertensive encephalopathy.

          -  Significant vascular disease.

          -  Clinically significant cardiovascular disease.

          -  Baseline left ventricular ejection fraction by multiple-gated acquisition scan or
             echocardiogram for subjects with prior exposure to anthracyclines not within
             institutional normal limits.

          -  Symptomatic peripheral vascular disease.

          -  History of high dose chemotherapy with bone marrow transplant or peripheral blood stem
             cell transplant within the previous 2 years.

          -  Evidence of bleeding diathesis or coagulopathy.

          -  Prior treatment with an epothilone or any antiangiogenic agent.

          -  Concurrent nonhealing wound, ulcer, or fracture.

          -  Any current or history of brain and/or leptomeningeal metastases. Psychiatric
             disorders or other conditions rendering the participant incapable of complying with
             the requirements of the protocol.

          -  Any concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in
             situ of the cervix.

          -  Known allergy to any of the study drugs or their excipients.