A Phase II Open Label, Randomized, 3 Arm Trial of 2 Schedules of Ixabepilone Plus Bevacizumab and Paclitaxel Plus Bevacizumab as First Line Therapy for Locally Recurrent or Metastatic Breast Cancer
- 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
- 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.
- 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
- 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.