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A Randomized Phase III Tial Of Paclitaxel Versus Paclitaxel Plus Bevacizumab (rhuMAb VEGF) As First-Line Therapy For Locally Recurrent or Metastatic Breast Cancer

Phase 3
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Randomized Phase III Tial Of Paclitaxel Versus Paclitaxel Plus Bevacizumab (rhuMAb VEGF) As First-Line Therapy For Locally Recurrent or Metastatic Breast Cancer


- Compare the time to treatment failure in patients with locally recurrent or metastatic
breast cancer treated with paclitaxel with or without bevacizumab.

- Compare the objective response rate, duration of response, overall survival, and time
to progression in patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
according to disease-free interval (no more than 24 months vs more than 24 months), number
of metastatic sites (less than 3 vs 3 or more), treatment with prior adjuvant chemotherapy
(yes vs no), and estrogen receptor status (positive vs negative vs unknown). Patients are
randomized to one of two treatment arms.

- Arm I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 followed by
bevacizumab IV over 30-90 minutes on days 1 and 15.

- Arm II: Patients receive paclitaxel as in arm I. In both arms, courses repeat every 4
weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and on day 1 of weeks 17 and 33.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually thereafter.

PROJECTED ACCRUAL: A total of 316-650 patients (158-325 per treatment arm) will be accrued
for this study within 31 months.

Inclusion Criteria


- Histologically or cytologically confirmed adenocarcinoma of the breast

- Locally recurrent disease that is not amenable to surgical resection with curative
intent OR

- Metastatic disease

- No HER-2-overexpressing (3+) breast cancer unless previously treated with trastuzumab

- Unknown HER-2 status allowed provided herceptin-based therapy inappropriate or
not indicated

- No prior or radiologic evidence of CNS metastases, including previously treated,
resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan
or MRI

- Hormone receptor status:

- Not specified



- 18 and over


- Male or female

Menopausal status:

- Not specified

Performance status:

- ECOG 0-1

Life expectancy:

- Not specified


- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No prior bleeding diathesis


- Bilirubin no greater than 1.5 mg/dL

- SGOT no greater than 2 times upper limit of normal (ULN) (5 times ULN for known liver

- PT/PTT no greater than 1.5 times normal

- INR no greater than 1.5 times normal


- Creatinine no greater than 2.0 mg/dL

- No proteinuria by dipstick urinalysis

- Trace proteinuria allowed

- Proteinuria less than 500 mg by 24-hour urine collection if proteinuria at least 1+
by urinalysis


- No clinically significant cardiovascular disease

- No myocardial infarction within the past 12 months

- No unstable angina

- No prior deep vein thrombosis

- No grade 2 or greater peripheral vascular disease

- No uncontrolled congestive heart failure

- No uncontrolled hypertension (systolic blood pressure greater than 170 mmHg and
diastolic blood pressure greater than 95 mm Hg)

- No prior cerebrovascular accident


- No prior pulmonary embolism


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective non-hormonal contraception

- No history of seizures

- No non-healing wound or fracture

- No hypersensitivity to paclitaxel, Cremophor EL, Chinese hamster ovary cell products,
or other recombinant human antibodies

- No active infection requiring parenteral antibiotics


Biologic therapy:

- See Disease Characteristics


- No prior chemotherapy for locally recurrent or metastatic breast cancer

- At least 12 months since prior adjuvant or neoadjuvant taxane therapy

- At least 3 weeks since prior adjuvant chemotherapy

Endocrine therapy:

- At least 3 weeks since prior hormonal therapy for locally recurrent or metastatic
breast cancer


- At least 3 weeks since prior radiotherapy

- No prior radiotherapy to only site of disease

- No concurrent local radiotherapy for pain control or life-threatening situations
(e.g, superior vena cava syndrome, spinal cord compression, or CNS metastases)


- At least 4 weeks since prior major surgical procedure except placement of vascular
access device or breast biopsy

- At least 7 days since prior minor surgical procedure, including placement of an
access device or fine needle aspiration


- At least 10 days since prior anticoagulant therapy (low-dose anticoagulant therapy to
maintain patency of a vascular access device allowed)

- At least 10 days since prior and no concurrent daily aspirin (more than 325 mg/day)
or other non-steroidal anti-inflammatory medication known to inhibit platelet

- No concurrent dipyridamole, ticlopidine, clopidogrel, or cilostazol

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-Free Survival

Outcome Time Frame:

Assessed every 3 months for 2 years, then every 6 months for 3 years

Safety Issue:


Principal Investigator

Kathy Miller, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Indiana University Melvin and Bren Simon Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2001

Completion Date:

May 2009

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • male breast cancer
  • Breast Neoplasms



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