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A Randomized Phase III 2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab for the First-line Treatment of HER2-negative Locally Recurrent or Metastatic Breast Cancer

Phase 3
18 Years
Open (Enrolling)
Metastatic Breast Cancer

Thank you

Trial Information

A Randomized Phase III 2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab for the First-line Treatment of HER2-negative Locally Recurrent or Metastatic Breast Cancer

Arm A:

Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks

Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks

Arm B:

Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks

Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks

In both arms treatment will be given until first disease progression (PD), unacceptable
toxicity or withdrawal of patient consent.

For patients who stop chemotherapy for any reason before PD (e.g. toxicity) the other
treatment should be given as monotherapy until PD.

Inclusion Criteria

- Written informed consent

- Age ≥18 years

- Able to comply with the protocol

- Histologically or cytologically confirmed, HER2-negative, adenocarcinoma of the
breast with measurable or non-measurable locally recurrent or metastatic disease

- ECOG performance status of 0-2

- Life expectancy more than 12 weeks

- Prior (neo)adjuvant chemotherapy is allowed provided that the last dose of
chemotherapy was more than 6 months prior to randomization, if (neo)adjuvant Therapy
was Taxane-based, patients are eligible only if they received their last taxane more
than 12 months prior to randomization.

- Prior adjuvant radiotherapy is allowed as part of the treatment of early breast
cancer If the last fraction of radiotherapy occurred at least 6 months prior to
randomization. Radiotherapy administered solely for the relief of metastatic bone
pain is allowed prior to study entry, the last fraction of radiotherapy was
administered ≥ 3 weeks prior to randomization.

- Adequate left ventricular ejection function

- Adequate hematological function

- Adequate liver function

- Adequate renal function

- The use of full-dose oral or parenteral anticoagulants is permitted as long as the
patient has been on a stable level of anticoagulation for at least two weeks at the
time of randomization

Exclusion Criteria:

- Previous chemotherapy for metastatic or locally recurrent breast cancer

- Concomitant hormonal therapy for locally recurrent or metastatic disease. Previous
hormonal therapy must have been discontinued at least 3 weeks prior to randomization

- Previous radiotherapy for the treatment of metastatic disease

- Other primary tumors within the last 5 years, except for adequately controlled basal
cell carcinoma of the skin, or carcinoma in situ of the cervix.

- Pre-existing peripheral neuropathy NCI CTCAE grade > 2 at randomization.

- Evidence of spinal cord compression or current evidence of CNS

- History or evidence upon physical/neurological examination of CNS disease unrelated
to cancer, unless adequately treated with standard medical therapy (e.g. uncontrolled

- Major surgical procedure, open biopsy or significant traumatic injury within 28 days
prior to randomization, or anticipation of the need for major surgery during the
course of the study treatment

- Minor surgical procedures, including insertion of an indwelling catheter, within 24
hours prior to randomization

- Current or recent (within 10 days of first dose of bevacizumab) use of aspirin or

- Chronic daily treatment with History or evidence of inherited bleeding diathesis or

- Uncontrolled hypertension

- Clinically significant cardiovascular disease, requiring medication during the study
and might interfere with regularity of the study treatment, or not controlled by

- Non-healing wound, active peptic ulcer or bone fracture

- History of abdominal fistula or any grade 4 non-gastrointestinal fistula,
gastrointestinal perforation or intra-abdominal abscess within 6 months of

- Active infection requiring i.v. antibiotics at randomization.

- Pregnant or lactating females, Women of childbearing potential,not using

- Men who do not agree to use contraception

- Current or recent (within 28 days of randomization) treatment with another
investigational drug or participation in another investigational study

- Clinically significant malabsorption syndrome or inability to take oral medication

- Psychiatric disability

- Requirement for concurrent use of the antiviral agent sorivudine or chemically
related analogues. Evidence of any other disease, metabolic or psychological
dysfunction, physical examination finding, or clinical laboratory finding giving
reasonable suspicion of a disease or condition that contraindicates the use of an
investigational drug

- Known DPD deficiency or prior unanticipated severe reaction to fluoropyrimidine

- Known hypersensitivity to any of the study drugs or excipients

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To show non-inferiority of Arm B versus Arm A in terms of overall survival (OS). Overall survival is assessed from randomization until date of death.

Outcome Time Frame:

until date of death

Safety Issue:


Principal Investigator

Christoph C Zielinski, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dep. of Internal Medicin I, Oncology, Medical University of Vienna


Austria: Agency for Health and Food Safety

Study ID:




Start Date:

April 2008

Completion Date:

November 2013

Related Keywords:

  • Metastatic Breast Cancer
  • Breast Neoplasms