Primary Systemic Therapy in Operable/Locally Advanced Breast Cancer

Phase 2

Completed

Conditions: Breast Cancer

Interventions: Drug: Bevacizumab
Drug: Cyclophosphamide
Drug: Docetaxel

Registration Number: NCT00203502

Lead Sponsor: University of Arkansas

Brief Summary: The main purpose of this study is to find out what effects taking the drug bevacizumab together with two chemotherapeutic agents, docetaxel and cyclophosphamide followed by doxorubicin alone before surgery will on breast cancer. Bevacizumab will be given for twelve weeks in combination with chemotherapy then it ill be held during the administration of doxorubicin. Twenty-eight to fifty-six days after undergoing surgery, all patients will receive nine three-weekly infusions of bevacizumab.

Detailed Description: Prior to being enrolled in this study, they will undergo an evaluation to determine eligibility. The study doctor will obtain a complete medical history, complete a physical examination including blood pressure and heart rate. The doctor will also obtain a baseline ECG as well as blood tests (approximately two tablespoons of blood). In order to decrease the effects of food, exercise and the sleep/wake cycle variability, all blood samples must be taken between 8AM - 10AM and patients will need to fast (no food or drink) for 10 hours prior to the blood test. Patients will also need to strain from working out prior to the blood test. The study will ask for a list of current medications. Patients will not be eligible if they have a history of or now require long-term anticoagulant (blood thinner) therapy (i.e. Coumadin or anything patients may be taking to prevent blood clots) have an allergy to bevacizumab or any other drugs used in the study.

Many of the following evaluations are commonly done to determine diagnosis and/or stage of breast cancer and may have already had some of all of them done. If the following procedures were not done within three weeks, they will need to be done again prior to receiving any study therapy.

* Diagnosis of breast cancer by fine needle aspiration or core needle biopsy will be required for entry in this study.

* Clip Placement - a clip will be placed in the tumor during the core biopsies as a marker to assist surgeons at the time of surgery.

* Tumor Clip Placements - a caliper is similar to a ruler and is used to measure the tumor from the outside of the body instead of always having to use an ultrasound or MRI.

* Tumor Ultrasound - this is a non-invasive exam that uses sound waves to produce a picture of your tumor.

All study participants will be treated with bevacizumab 15 mg/kg plus docetaxel 75 mg/m2 and cyclophosphamide 500 mg/m2 every three weeks for a total of four treatments. Three weeks after the completion of this part of the treatment patients will start receiving doxorubicin 60 mg/m2 every three weeks for a total of four treatments. All these drugs will be given as intravenous infusion on the first day of each three-week period.

Patients will come in for every three week visits and have a physical exam including blood pressure and heart rate. Medications lists will be taken and any side effects that may have been experienced. Tumor caliper measurements will be done and blood will be drawn at each of these visits.

A mammogram and MUGA scan will be done again just prior to surgery. Patients will undergo tumor surgery approximately six months after treatment. Patients will need to visit the study physician one month after surgery for another physical examination including blood pressure and heart rate, an assessment of any side effects and a list of current medications.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 40

Inclusion Criteria

The diagnosis of breast cancer established by biopsy.
Normal kidney function
Normal LVEF evaluated by MUGA Scan
>18 years of age
Good performance status defined by ECOG scale of 0 or 1
Consent
Women of childbearing potential must have a negative pregnancy test.
Use of effective means of contraception in subjects of child-bearing potential while on treatment and for at least 3 months thereafter.
Peripheral Neuropathy: must be < grade 1
Hematologic (minimal values)
Absolute neutrophil count >1,500/mm3
Hemoglobin >8.0 g/dl
Platelet count >100,000/mm3
Hepatic
Total bilirubin <ULN
AST, ALT, Alkaline Phosphatase must be within range

Exclusion Criteria

Patients with locally advanced breast cancer with skin ulcerations
Stage IV breast cancer
Inflammatory breast cancer
Allergy to any component of the treatment regimen
Women who are breast feeding
Pregnancy or refusal to use effective contraception
Inability to comply with study and/or follow-up procedures.
Current, recent, or planned participation in a experimental drug study
Blood pressure of >150/100 mmHg. Essential hypertension well controlled with anti hypertensives is not an exclusion criterion.
unstable angina
New York Heart Association Grade II or greater congestive heart failure
history of myocardial infarction within 6 months
history of stroke within 6 months
Clinical significant peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Presence of central nervous system or brain metastasis
major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0
Minor surgical procedure such as fine needle aspirations or core biopsy within 7 days prior to day 0
Pregnant or lactating
Urine protein: creatinine ratio >1.0 at screening
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
Serious, non-healing wound, ulcer, or bone fracture

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention: Dtx Cyclophosphamide Bev	Bevacizumab	Docetaxel 75m/m2 Cyclophosphamide 500 mg/m2 Bevacizumab 15 mg/kg
Intervention: Dtx Cyclophosphamide Bev	Cyclophosphamide	Docetaxel 75m/m2 Cyclophosphamide 500 mg/m2 Bevacizumab 15 mg/kg
Intervention: Dtx Cyclophosphamide Bev	Docetaxel	Docetaxel 75m/m2 Cyclophosphamide 500 mg/m2 Bevacizumab 15 mg/kg

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Pathological Complete Response.	Participants were assessed during surgery, an average of one hour	Pathological complete response was defined as the absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the resected breast.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Complete Response in Breast and the Axillary Lymph Nodes After the Completion of Chemotherapy and Bevacizumab.	At completion of chemotherapy treatment, an average of one hour	Clinical complete response was defined using RECIST response categories as the clinical response to chemotherapy
Percentage of Participants With Grade 3 or 4 Adverse Events	After each chemotherapy infusion, approximately one hour	Percent of participants who had at least one grade 3 or 4 adverse event
To Measure the Change in Left Ventricular Ejection Fraction (LVEF) From Baseline	Immediately before treatment and 1 year after start of treatment	Absolute change in LVEF, where LVEF values are measured in percentage units
Percentage of Participants With Pathologic Complete Response (pCR) Among Those With Triple Negative Breast Cancer	at surgery, one day	pCR rate for triple negative patients--percent