Imetelstat in Combination With Paclitaxel (With or Without Bevacizumab) in Patients With Locally Recurrent or Metastatic Breast Cancer

Patients will be randomized in a 1:1 ratio to imetelstat + paclitaxel (with or without bevacizumab) versus paclitaxel (with or without bevacizumab) alone.

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast that is either locally recurrent or metastatic. Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent
• Either have not received chemotherapy or may have had one prior non-taxane chemotherapy regimen for metastatic disease (there are no restrictions on prior hormonal therapy)
• Prior use of bevacizumab is allowed provided that it was not administered in combination with a taxane
• ECOG performance status 0-1
• Adequate bone marrow reserve as indicated by:

• ANC > 1500/uL (without use of growth factors within 7 days)
• Platelet count > 100,000 (without transfusion in prior 7 days)
• Hemoglobin > 9.0 g/dL

Exclusion criteria

• Women who are pregnant or breast feeding
• Locally recurrent disease amenable to resection with curative intent
• HER-2-positive breast cancer
• Active central nervous system (CNS) metastatic disease including those patients receiving radiotherapy and/or steroid treatment (within the last 3 months)
• Prior adjuvant or neoadjuvant taxane chemotherapy within 12 months prior of first relapse
• Investigational therapy within 4 weeks of first study drug administration
• Prior radiation, cytotoxic, or hormonal therapy within 2 weeks of first study drug administration
• Therapeutic anti-coagulation or regular use of anti-platelet therapy within 2 weeks prior to first study drug administration (low dose anti-coagulant therapy to maintain patency of a vascular access device is allowed)
• Grade ≥ 2 neuropathy
• Uncontrolled clinically significant atrial or ventricular arrhythmias (unless pacemaker in place)
• Severe conduction disturbance including clinically significant QTC prolongation > 450 ms (unless pacemaker in place)
• Active or chronically recurrent bleeding (e.g., active peptic ulcer disease)
• Clinically relevant active infection
• Known positive serology for human immunodeficiency virus (HIV)