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A Phase II Safety and Tolerability Study of Avastin When Added to Single-agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Phase II Safety and Tolerability Study of Avastin When Added to Single-agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain

There is an unmet clinical need for effective therapy of breast cancer that has metastasized
to the brain. In this scenario, median survival is around 12 months using currently
available therapeutic interventions. The majority of chemotherapy-based clinical trials
have considered the presence of central nervous system metastasis an exclusion criterion due
to the risk of toxicities, the inability of chemotherapeutic agents to cross the blood brain
barrier, and the limited overall survival within this patient population.

The preclinical data regarding the safety and activity of bevacizumab in VEGF-expressing
tumors provide a good rationale for its study in patients with breast cancer with metastasis
to the brain. Yano, et al. illustrated that tumor cell expression of VEGF mRNA and protein
directly correlated with angiogenesis and growth of brain metastasis in a nude mouse model.
Transfecting the experimental cell lines known to produce visceral metastasis with an
anti-sense VEGF-gene significantly reduced the incidence of brain metastasis. Kim, et al.
illustrated that a murine model specific for brain metastases originating from breast cancer
showed elevated expression of the angiogenic and permeability-inducing factor VEGF-A. The
growth of the brain metastases in this model was attenuated by the addition of a
VEGF-tyrosine kinase inhibitor via induction of apoptosis and decreased angiogenesis. VEGF
has also been implicated in the development of brain edema, a significant source of the
morbidity and mortality associated with brain metastasis. Enhanced levels of VEGF and its
receptors have been reported in a murine model after induction of cortical ischemia.
Finally, antagonism of VEGF was demonstrated to reduce both immediate and delayed volume of

The optimal dose of bevacizumab has been extensively studied in phase I trials alone and in
combination with chemotherapy. The safe and effective dose has been established as 10 mg/kg
q 14 days or 15 mg/kg Q 21 days. In addition to irinotecan and paclitaxel, it has been
previously used in phase II/III settings in combination with capecitabine, vinorelbine,
gemcitabine, and docetaxel. Phase III studies showed an overall survival advantage when
bevacizumab was added to an irinotecan/5FU-based regimen for metastatic colorectal cancer,
and when added to weekly paclitaxel for metastatic breast cancer.

Inclusion Criteria:

- Female, 18+, with evaluable metastatic breast cancer and stable brain metastases

- Must have received definitive radiotherapy

- No evidence, or history of, central nervous system hemorrhage

- Adequate organ and hematological function

Exclusion Criteria:

- Active infection, non-healing wound, or history of any bleeding diathesis or

- Uncontrolled hypertension, congestive heart failure, peripheral vascular disease

Type of Study:


Study Design:

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

Outcome Measure:

• Safety and Tolerability In this study, safety and tolerability will be assessed according to standard (CTCAE version 3.0) toxicity reporting criteria. Adverse events will be monitored at every patient visit and quality of life will be measured at ba

Outcome Time Frame:

May 2009

Safety Issue:


Principal Investigator

Kimberly Blackwell, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

May 2011

Related Keywords:

  • Breast Cancer
  • Breast Cancer
  • Metastatic
  • Brain
  • Anti-angiogenesis
  • Breast Neoplasms
  • Brain Neoplasms



Virginia Oncology Associates Newport News, Virginia  23606
Duke University Medical Center Durham, North Carolina  27710
Palm Beach Cancer Center Institute West Palm Beach, Florida  33401-3406
Presbyterian Health Care Charlotte, North Carolina  28204