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A Pilot Study of Bevacizumab With Dose Dense Doxorubicin and Cyclophosphamide (AC) Followed by Dose Dense Nanoparticle Albumin Bound Paclitaxel for the Treatment of Early Stage Breast Cancer

18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

A Pilot Study of Bevacizumab With Dose Dense Doxorubicin and Cyclophosphamide (AC) Followed by Dose Dense Nanoparticle Albumin Bound Paclitaxel for the Treatment of Early Stage Breast Cancer



- Determine the cardiac safety of adjuvant concurrent bevacizumab and dose-dense
doxorubicin hydrochloride and cyclophosphamide followed by dose-dense paclitaxel
albumin-stabilized nanoparticle formulation and maintenance therapy comprising
bevacizumab alone in patients with early-stage breast cancer.


- Determine the noncardiac toxicity of this regimen in these patients.

- Determine the efficacy of this regimen, in terms of time to tumor recurrence and
overall survival, in these patients.

- Explore changes in circulating endothelial cells and circulating tumor cells from
pre-treatment levels in patients with no evidence of disease.

- Prospectively explore the use of serial troponin I as a predictor of cardiac toxicity
in patients treated with this regimen.

- Prospectively explore the relationship between plasma renin activity and hypertension
in patients treated with bevacizumab and chemotherapy.

OUTLINE: This is a nonrandomized, pilot, multicenter study.

Patients receive doxorubicin hydrochloride IV, cyclophophamide IV, and bevacizumab IV over
30-90 minutes on day 1 and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats
every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30
minutes on day 1 and pegfilgrastim SC on day 2. Treatment with paclitaxel albumin-stabilized
nanoparticle formulation and pegfilgrastim repeats every 2 weeks for 4 courses in the
absence of disease progression or unacceptable toxicity. Patients then receive maintenance
therapy comprising bevacizumab IV over 30-90 minutes on day 1. Treatment with maintenance
therapy repeats every 3 weeks for 12 courses in the absence of disease progression or
unacceptable toxicity.

Blood samples are collected at baseline and periodically during study treatment. Samples are
analyzed for circulating endothelial cells (by flow cytomery [FC]), circulating epithelial
cells (by immunocytochemistry and FC), troponin I concentrations (by enzyme immunoassay or
chemiluminescent microparticle immunoassay), and plasma renin activity (by

After completion of study treatment, patients are followed every 4-6 months for 3 years,
every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Inclusion Criteria


- Histologically or cytologically confirmed invasive breast cancer meeting the
following criteria:

- Early-stage disease

- No stage IV disease

- More than one synchronous primary breast tumor

- Lymph node positive OR high-risk lymph node negative

- Candidate for treatment with anthracycline- and taxane-based chemotherapy in the
adjuvant setting

- Must begin therapy within 84 days after the final required surgical procedure

- HER2/neu-negative breast cancer, defined as an immunohistochemistry (IHC) score of 0,
1+ or 2+ and fluorescent in situ hybridization (FISH) not amplified

- No CNS disease (e.g., primary brain tumor or brain metastasis)

- Hormone receptor status known


- Male or female

- Pre- or post-menopausal

- ECOG performance status 0-1

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin normal

- AST or ALT ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Urine protein:creatinine ratio ≤ 1.0

- PT and PTT normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after
completion of study therapy

- LVEF normal by MUGA scan at baseline

- No significant bleeding within the past 6 months

- No uncontrolled underlying bleeding diathesis

- No nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would
preclude study therapy, including any of the following conditions:

- Blood pressure > 150/100 mm Hg

- Unstable angina

- New York Heart Association class II -IV congestive heart failure

- Myocardial infarction or stroke within the past 12 months

- Clinically significant peripheral vascular disease

- No seizures not controlled with standard medical therapy

- No history of stroke

- No known allergy or hypersensitivity to study drugs (prior hypersensitivity to
paclitaxel allowed)

- No significant traumatic injury within the past 28 days

- No serious nonhealing wound, ulcer, or bone fracture

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No active gastroduodenal ulcer

- No uncontrolled intercurrent illness, including psychiatric illness or social
situation that would limit compliance with study requirements


- See Disease Characteristics

- Prior therapy for an ipsilateral or contralateral breast cancer primary allowed
provided the following criteria are met:

- No prior anthracycline therapy

- Prior hormonal therapy for this previous breast cancer is allowed, but must be
stopped during study therapy

- At least 1 year since prior taxane therapy

- More than 28 days since prior and no concurrent major surgery or open biopsy

- Anticipated reconstructive surgery (e.g., tissue expander exchange) is allowed
during the course of the study (bevacizumab will be held during that time as per
protocol guidelines)

- More than 7 days since prior minor surgery, including fine-needle aspiration or core

- At least 24 hours since prior indwelling catheter placement

- No prior bevacizumab or other KDR inhibitors (e.g., VEGF Trap, semaxanib, SU6668,
vandetanib, vatalanib, AEE788, or IMC-1CII)

- No concurrent full-dose anticoagulation therapy

- No concurrent hormonal therapy as chemoprevention

- Concurrent participation in adjuvant hormone therapy or correlative or companion
(e.g., bisphosphonate clinic) studies allowed

- No other concurrent anticancer therapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Maura N. Dickler, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

July 2006

Completion Date:

Related Keywords:

  • Breast Cancer
  • male breast cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • Breast Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021