Study Evaluating the Safety and Efficacy of Onartuzumab (Metmab) And/Or Bevacizumab in Combination With Paclitaxel in Patients With Metastatic, Triple Negative Breast Cancer

• Objective response [ Time Frame: Complete or partial response maintained >/= 4 weeks. ] [ Designated as safety issue: No ]
• Duration of response [ Time Frame: Initial complete or partial response to disease progression or death on study from any cause, whichever occurs first. ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: Randomization to death from any cause. ] [ Designated as safety issue: No ]

• Objective response [ Time Frame: Complete or partial response maintained ≥ 4 weeks. ] [ Designated as safety issue: No ]
• Duration of response [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]

This is a randomized, Phase II, double-blind, multicenter, placebo controlled trial designed to preliminarily estimate the efficacy and evaluate the safety and tolerability of MetMAb + bevacizumab + paclitaxel and MetMAb + placebo + paclitaxel versus placebo + bevacizumab + paclitaxel in patients with metastatic or locally recurrent, triple-negative breast cancer who either have not received treatment (first line) or have progressed after one conventional cytotoxic chemotherapy regimen (second-line).

• Drug: bevacizumab
  Intravenous repeating dose
• Drug: MetMAb
  Intravenous repeating dose
• Drug: paclitaxel
  Intravenous repeating dose
• Drug: placebo
  Intravenous repeating dose

• Experimental: A
  Interventions:

  • Drug: bevacizumab
  • Drug: MetMAb
  • Drug: paclitaxel
• Placebo Comparator: B
  Interventions:

  • Drug: bevacizumab
  • Drug: paclitaxel
  • Drug: placebo
• Placebo Comparator: C
  Interventions:

  • Drug: MetMAb
  • Drug: paclitaxel
  • Drug: placebo

Inclusion Criteria:

• Women age >/= 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Histologically confirmed ER-, PR-, and HER2-negative (triple-negative) adenocarcinoma of the breast
• Confirmed availability of tumor tissue

Exclusion Criteria:

• Prior therapy with two or more regimens for metastatic breast cancer
• Any systemic anti-cancer therapy within 3 weeks prior to Day 1 of Cycle 1
• Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Day 1 of Cycle 1
• Prior therapy with a taxane for metastatic breast cancer
• Prior therapy with bevacizumab, sorafenib, sunitinib, or other putative VEGF pathway-targeted therapy following diagnosis of breast cancer
• Prior therapy with hormones and/or trastuzumab
• Inadequate hematology, renal, or hepatic organ function

Bevacizumab exclusion criteria

• Uncontrolled hypertension (systolic pressure > 150 mmHg and/or diastolic pressure > 100 mmHg), with or without anti-hypertensive medication
• Evidence of bleeding diathesis or coagulopathy