Know Cancer

forgot password

Phase II Trial of Primary Systemic Therapy for Locally Advanced Breast Cancer Using Sequential Doxil, Paclitaxel, and Cyclophosphamide With Concurrent Avastin

Phase 2
19 Years
Open (Enrolling)
Invasive Breast Cancer

Thank you

Trial Information

Phase II Trial of Primary Systemic Therapy for Locally Advanced Breast Cancer Using Sequential Doxil, Paclitaxel, and Cyclophosphamide With Concurrent Avastin

In this trial, an attempt will be made to replicate the high rate of complete pathological
response in patients with locally advanced breast cancer with a regimen in which Doxil is
substituted for conventional doxorubicin. We expect that the low or minimal effect on
cardiac function produced by Doxil will minimize any additional risk of cardiotoxicity from
Avastin. We will also measure left ventricular ejection fractions before and after
treatment to see if the substantial rate of subclinical cardiotoxicity reported by Swain et
al5 and Perez et al7 can be avoided. The reported rates of cardiotoxicity after treatment
with relatively high doses of Doxil are substantially lower than those of doxorubicin; few
data are available to estimate the rate of cardiotoxicity of Doxil in patients treated with
only about 100 mg/m2 total accumulated dose, the dose to be utilized here. The drug has
been used in a few patients in the primary systemic therapy setting, with no reported
clinical cardiotoxicity.

The expectation is that clinical and subclinical rates of cardiotoxicity will be very low or
negligible at the total doses to be used here.

Inclusion Criteria:

- Histologically confirmed, measurable, invasive breast carcinoma T >2cm, Nany, M0.

- Patients with node-negative, ER or PR-positive tumors ≤4 cm in size whose tumors are
low risk (defined as a score of 0-17) on an Oncotype DX profile are not eligible.

- 19 years of age or greater

- Known ER, PR and HER-2 status (FISH assay to be done on specimens with 2+ or 3+
immunohistochemical staining for HER-2): patients with gene amplification on FISH
study will be considered to be HER-2 positive. Patients for this study must be FISH
negative if immunohistochemical stain is 2+ or 3+ positive; patients with negative, 0
or 1+ immunohistochemical stain for HER-2 are eligible.

- Known axillary nodal status: aspiration cytology or biopsy

- Documented menopausal status premenopausal (having menstrual periods or FSH <35) or
postmenopausal (≥12 months since last menstrual period with intact uterus and at
least one ovary or FSH ≥35 or previous bilateral oophorectomy

- Non-pregnant if premenopausal (negative serum or urine pregnancy test within 7 days
of starting chemotherapy) and not breast feeding

- Patients with reproductive potential must use an adequate contraceptive method (e.g.,
abstinence, intrauterine device, barrier device with spermicide or surgical
sterilization) during treatment and for three months after completing treatment.

- Life expectancy of less than 12 weeks

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored Avastin
cancer study

- Pregnant or lactating women.

- History of cardiac disease, with New York Heart Association Grade II or greater or
clinical evidence of congestive heart failure.

- Serious comorbid medical conditions which would impair the ability to receive
chemotherapy on time

- Previous invasive cancer within the last 5 years

- Altered mental status or dementia which would interfere with understanding of
informed consent and ability to comply with study and follow-up procedures.

- Hypersensitivity to Doxil, doxorubicin, cyclophosphamide, cremaphore (contained in
teniposide, cyclosporine, and vitamin K), or to any component of Avastin

- Inadequately controlled hypertension (defined as blood pressure of >150/100 mmHg on
antihypertensive medication)

- Unstable angina pectoris

- History of myocardial infarction or unstable angina within 12 months prior to
beginning therapy

- History of stroke or TIA at any time

- Clinically significant vascular (e.g., aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis, aortic dissection) or peripheral vascular
disease with 6 months prior to beginning therapy

- History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per
episode) within 1 month prior to beginning therapy

- Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation)

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

- Patients must have a 2-d echocardiogram indicating an ejection fraction of > 50%
within 42 days prior to first dose of study drug. The method used at baseline must be
used for later monitoring.

- No distant metastases on bone scan and on CT scans of chest and abdomen (no
metastasis on optional PET scan is an acceptable alternative; if PET scan is done for
any reason it must show no evidence of distant metastasis). Baseline PET scan is
recommended but not required for all patients.

- No CNS metastasis

- Hbg ≥9 gm, platelets ≥100,000, granulocytes ≥1000, total or direct bilirubin ≤1.2,
creatinine ≤2.0 and urine protein:creatinine ratio <1.0

- No prior chemotherapy or radiotherapy and ≤4 weeks of prior antiestrogen or aromatase
inhibitor therapy

- No concomitant hormone replacement (i.e. estrogen or progestin) therapy

- PS less than or equal to one

Exclusion Criteria:

- Minor surgical procedure (excluding placement of a vascular access device) such as
fine needle aspiration or core needle biopsy within 7 days of beginning therapy

- Urine protein:creatinine ratio ≥1.0 at initial screening

- Known hypersensitivity to any component of Avastin

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months of beginning therapy

- Serious, non-healing wound, active ulcer, or untreated bone fracture

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- Known CNS metastasis, except for treated brain metastasis. Treated brain metastases
are defined as having no evidence of progression or hemorrhage after treatment and no
ongoing requirement for dexamethasone, as ascertained by clinical examination and
brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose)
are allowed. Treatment for brain metastases may include whole brain radiotherapy
(WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as
deemed appropriate by the treating physician. Patients with CNS metastases treated
by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1
will be excluded.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary endpoint will be the rate of achievement of complete pathological response, to be determined by findings at surgery, i.e., segmental or total mastectomy.

Outcome Description:

Frequency and proportion will be used to report the overall complete pathological response rate.

Outcome Time Frame:

After completion of at least 8 of the 9 chemotherapy doses.

Safety Issue:


Principal Investigator

John Carpenter, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Alabama at Birmingham


United States: Institutional Review Board

Study ID:




Start Date:

March 2008

Completion Date:

August 2017

Related Keywords:

  • Invasive Breast Cancer
  • Breast cancer
  • Breast Neoplasms



University of Alabama at Birmingham Birmingham, Alabama  35294-3300