A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2 Positive Metastatic Breast Cancer.

• Overall survival [ Time Frame: (36 months after randomization of last patient) ] [ Designated as safety issue: No ]
• Best overall response, duration of response, time to treatment failure. [ Time Frame: Event driven ] [ Designated as safety issue: No ]
• QoL, AEs, targeted events including CHF, laboratory parameters. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

This 2 arm study will compare the efficacy and safety of Avastin plus Herceptin/docetaxel, versus Herceptin/docetaxel alone, in patients with HER2 positive locally recurrent or metastatic breast cancer who have not received prior chemotherapy for their metastatic disease. Patients will be randomized 1:1 to receive either Avastin (15mg/kg iv q3weeks) + Herceptin (8mg/kg iv loading dose and 6mg/kg iv q3weeks maintenance) + docetaxel (100mg/m2 iv q3weeks) or Herceptin + docetaxel alone. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

• Drug: bevacizumab [Avastin]
  15mg/kg iv every 3 weeks
• Drug: Herceptin
  8mg/kg iv loading dose, followed by 6mg/kg iv every 3 weeks
• Drug: Docetaxel
  100mg/m2 iv every 3 weeks

• Experimental: 1
  Interventions:

  • Drug: bevacizumab [Avastin]
  • Drug: Herceptin
  • Drug: Docetaxel
• Active Comparator: 2
  Interventions:

  • Drug: Herceptin
  • Drug: Docetaxel

Inclusion Criteria:

• adult patients, >=18 years of age;
• HER2 positive breast cancer with locally recurrent or metastatic lesions;
• eligible for chemotherapy;
• baseline LVEF >=50%.

Exclusion Criteria:

• previous chemotherapy for metastatic or locally recurrent breast cancer;
• previous radiotherapy for metastatic breast cancer (except for metastatic bone pain relief);
• other primary tumor within last 5 years, with the exception of basal or squamous skin cancer, or in situ cancer of the cervix;
• clinically significant cardiovascular disease;
• chronic daily treatment with aspirin (>325mg/day) or clopidogrel (>75mg/day).