Primary Systemic Therapy in Operable/Locally Advanced Breast Cancer

May 2, 2016 updated by: University of Arkansas

Primary Systemic Therapy Using Sequential Docetaxel/Cyclophosphamide/Bevacizumab Followed by Doxorubicin in Operable/Locally Advanced Breast Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention: Dtx Cyclophosphamide Bev
Docetaxel 75m/m2 Cyclophosphamide 500 mg/m2 Bevacizumab 15 mg/kg
Drug: Bevacizumab
IV 15mg/kg 21 days
Other Names:
  • Avastin
Drug: Cyclophosphamide
500mg per meter squared, IV every 21 days
Other Names:
  • Cytoxan
Drug: Docetaxel
60 mg per meter squared, IV every 21 days
Other Names:
  • Taxotere
  • Adriamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Pathological Complete Response.
Time Frame: 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.
Participants were assessed during surgery, an average of one hour

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arkansas

Collaborators

Genentech, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 20, 2005

Study Record Updates

Last Update Posted (Estimate)

May 11, 2016

Last Update Submitted That Met QC Criteria

May 2, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UARK 2004-59

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe