Primary Systemic Therapy in Operable/Locally Advanced Breast Cancer

Overview[ - collapse ][ - ]

Purpose 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.
ConditionBreast Cancer
InterventionDrug: Bevacizumab/Avastin
Drug: Cyclophosphamide
Drug: Doxorubicin
PhasePhase 2
SponsorUniversity of Arkansas
Responsible PartyUniversity of Arkansas
ClinicalTrials.gov IdentifierNCT00203502
First ReceivedSeptember 12, 2005
Last UpdatedSeptember 17, 2013
Last verifiedSeptember 2013

Tracking Information[ + expand ][ + ]

First Received DateSeptember 12, 2005
Last Updated DateSeptember 17, 2013
Start DateSeptember 2005
Estimated Primary Completion DateNot Provided
Current Primary Outcome MeasuresTo evaluate the efficacy in terms of pathologic response of the combination of bevacizumab with docetaxel/cyclophosphamide followed by doxorubicin in women with operable/locally advanced breast cancer in the neo-adjuvant setting. [Time Frame: upon surgery] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • To evaluate clinical response in breast and the axillary lymph nodes after the completion of chemotherapy and bevacizumab. [Time Frame: end of treatment] [Designated as safety issue: No]
  • To evaluate the tolerability of the combination of bevacizumab with docetaxel/cyclophosphamide followed by doxorubicin in women with locally advanced breast cancer in the neo-adjuvant setting. [Time Frame: periodically] [Designated as safety issue: Yes]
  • To evaluate the safety of bevacizumab given post operatively in the adjuvant setting for 6 months. [Time Frame: 1 year after start of treatment] [Designated as safety issue: Yes]
  • To study the correlation of pathologic response with selected biological markers in the breast and lymph nodes. [Time Frame: at surgery] [Designated as safety issue: No]
  • The data collected from this study, such as response rate and safety information, will help design a phase III trial for final testing of the benefit of bevacizumab in this population. [Time Frame: upon study completion] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitlePrimary Systemic Therapy in Operable/Locally Advanced Breast Cancer
Official TitlePrimary Systemic Therapy Using Sequential Docetaxel/Cyclophosphamide/Bevacizumab Followed by Doxorubicin in Operable/Locally Advanced Breast Cancer
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.
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionBreast Cancer
InterventionDrug: Bevacizumab/Avastin
IV 15mg/kg 21 days
Drug: Cyclophosphamide
500mg per meter squared, IV every 21 days
Drug: Doxorubicin
60 mg per meter squared, IV every 21 days
Study Arm (s)Not Provided

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment40
Estimated Completion DateNot Provided
Estimated Primary Completion DateDecember 2013
Eligibility Criteria
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
- 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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00203502
Other Study ID NumbersUARK 2004-59
Has Data Monitoring CommitteeNo
Information Provided ByUniversity of Arkansas
Study SponsorUniversity of Arkansas
CollaboratorsGenentech
Investigators Principal Investigator: Issam Makhoul, MD University of Arkansas
Verification DateSeptember 2013

Locations[ + expand ][ + ]

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