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Breast CancerPhase 2NCT00365417

Therapy With Bevacizumab (BEV), Doxorubicin, and Cyclophosphamide Followed by BEV, Docetaxel, and Capecitabine Before Surgery Followed by BEV Alone After Surgery for Women With Locally Advanced Breast Cancer

A Phase 2 study testing Bevacizumab, Doxorubicin and Cyclophosphamide in people with Breast Cancer, run by NSABP Foundation Inc at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Bevacizumab is an angiogenesis inhibitor which means it works to stop blood vessel formation in tumors. Without new blood vessels, the growth of a tumor is slowed. Chemotherapy drugs kill cancer cells more directly. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Bevacizumab, Doxorubicin and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
Aug 2006to Nov 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be female.
  • The patient must be greater than/equal to 18 years old
  • The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy or limited incisional biopsy.
  • Patients must have clinical Stage IIIA, IIIB, or IIIC disease (American Joint Committee on Cancer [AJCC] staging criteria) with a primary breast tumor that is greater than/equal to 2.0 cm measured by clinical exam, unless the patient has inflammatory breast carcinoma, in which case measurable disease is not required.
  • Patients must have the ability to swallow oral medication.
  • The patient's Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1.
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  • At the time of study entry, blood counts must meet the following criteria:
  • Absolute neutrophil count (ANC) must be greater than/equal to 1200/mm3.
  • Platelet count must be greater than/equal to 100,000/mm^3.
  • Hemoglobin must be greater than/equal to 10 g/dL.
  • The following criteria for evidence of adequate hepatic function must be met:
  • total bilirubin must be less than/equal to upper limit of normal (ULN) for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
  • alkaline phosphatase must be less than 2.5 x ULN for the lab; and
  • aspartate aminotransferase (AST) must be less than/equal to 1.5 x ULN for the lab.
  • Alkaline phosphatase and AST may not both be greater than the ULN. For example, if the alkaline phosphatase is greater than the ULN but less than/equal to 2.5 x ULN, then the AST must be less than/equal to the ULN. If the AST is greater than the ULN but less than/equal to 1.5 x ULN, then the alkaline phosphatase must be less than/equal to ULN.
  • Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than/equal to 2.5 x ULN are eligible for inclusion in the study if a bone scan or positron emission tomography (PET) scan does not demonstrate metastatic disease. Patients with suspicious findings on bone scan or PET scan are eligible if suspicious findings are confirmed as benign by x-ray, magnetic resonance imaging (MRI), or biopsy.
  • Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging (computed tomography [CT], MRI, or PET scan) does not demonstrate metastatic disease and adequate hepatic function.
  • The following criteria for evidence of adequate renal function must be met:
  • Serum creatinine less than/equal to ULN for the lab.
  • Calculated creatinine clearance must be greater than 50 mL/min.
  • Urine protein/creatinine (UPC) ratio must be less than 1.0.
  • Patients must have their left ventricular ejection fraction (LVEF) assessed by multigated acquisition (MUGA) scan or echocardiogram within 3 months prior to study entry. The LVEF must be greater than/equal to the lower limit of normal (LLN) for the cardiac imaging facility performing the MUGA scan or echocardiogram. Note: If the cardiac imaging facility cannot provide a LLN, use 50% as the LLN value.
  • Note: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments to determine if bevacizumab therapy can be continued following doxorubicin and cyclophosphamide (AC) and postoperatively, it is critical that this baseline study be an accurate assessment of the patient's LVEF. If the baseline LVEF is greater than 65%, the MUGA scan or echocardiogram must be repeated prior to study entry. The lower of the two LVEF values should be used as the baseline LVEF.
  • Patients must have an electrocardiogram (EKG) within 3 months prior to study entry.

Who cannot join

  • Tumor determined to be strongly HER2-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
  • Excisional biopsy for this primary tumor.
  • Synchronous bilateral invasive breast cancer.
  • Surgical axillary staging procedure prior to study entry (Exceptions: 1) fine needle aspiration (FNA) of an axillary node is permitted for any patient, and 2) although not recommended, a sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted.)
  • History of any of the following cancers:
  • Ipsilateral breast cancer: invasive, ductal carcinoma in situ (DCIS) treated with any therapy other than excision
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  • Contralateral breast cancer: invasive within the past 5 years (Patients with history of DCIS or synchronous DCIS are eligible)
  • History of non-breast malignancies within the 5 years prior to study entry. Patients with the following cancers are eligible if diagnosed and treated within the previous 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Prior therapy with anthracyclines, taxanes, capecitabine, or bevacizumab for any malignancy.
  • Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to study entry. The only exception is hormonal therapy, which may have been given for up to a total of 28 days anytime after diagnosis and before study entry. In such a case, hormonal therapy must stop at or before study entry and be re-started, if indicated, following chemotherapy.
  • Any of the following cardiac conditions:
  • angina pectoris that requires the use of anti-anginal medication;
  • history of documented congestive heart failure;
  • serious cardiac arrhythmia requiring medication;
  • severe conduction abnormality;
  • valvular disease with documented cardiac function compromise; or
  • uncontrolled hypertension defined as blood pressure greater than 150/90 on antihypertensive therapy. (Patients with hypertension that is well controlled on medication are eligible.)
  • History of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function.
  • History of transient ischemic attack (TIA) or cerebrovascular accident (CVA).
  • History of other arterial thrombotic event within 12 months before study entry.
  • Symptomatic peripheral vascular disease.
  • Any significant bleeding within 6 months before study entry.
  • Serious or non-healing wound, skin ulcers, or bone fracture.
  • Gastroduodenal ulcer(s) determined by endoscopy to be active.
  • Invasive procedures defined as follows:
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to planned start of study therapy. (Note: Placement of a vascular access device is not considered a major surgical procedure.)
  • Anticipation of need for major surgical procedures (other than the required breast surgery) during the course of the study.
  • Known bleeding diathesis or coagulopathy. (Patients on warfarin with an in-range international normalized ratio [INR] [usually between 2 and 3] are eligible.)
  • Other nonmalignant systemic disease (cardiovascular, renal, hepatic, diabetes, etc.) that would preclude the patient from receiving study treatment or would prevent required follow-up.
  • Sensory/motor neuropathy greater than/equal to grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0).
  • Conditions that would prohibit administration of corticosteroids.
  • History of hypersensitivity reaction to drugs formulated with polysorbate 80.
  • Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention. Patients are eligible only if these medications are discontinued prior to study entry.
  • Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. These patients are eligible if this therapy is discontinued prior to study entry. (Women of reproductive potential must agree to use an effective non-hormonal method of contraception during study therapy and for at least 3 months after completion of bevacizumab.)
  • Pregnancy or lactation at the time of study entry.
  • Use of any investigational agent within 4 weeks prior to enrollment in the study.
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • NSABP Foundation, Inc.

    Pittsburgh, Pennsylvania, 15212

Other trials in United States

About this study

Official title: A Phase II Clinical Trial of Bevacizumab Beginning Concurrently With a Sequential Regimen of Doxorubicin and Cyclophosphamide Followed by Docetaxel and Capecitabine as Neoadjuvant Therapy Followed by Postoperative Bevacizumab Alone for Women With Locally Advanced Breast Cancer

Bevacizumab is an angiogenesis inhibitor which means it works to stop blood vessel formation in tumors. Without new blood vessels, the growth of a tumor is slowed. Chemotherapy drugs kill cancer cells more directly. This study will evaluate:

  • How bevacizumab, given with chemotherapy before surgery, and then bevacizumab given alone after surgery, will affect locally advanced breast tumors
  • Side effects from adding bevacizumab to chemotherapy
  • Whether adding bevacizumab to chemotherapy for breast cancer will affect the heart
  • If receiving bevacizumab will have any effect on how patients recover from surgery
  • Side effects of the combinations of drugs used in this study
Read the detailed description

Initial trials of neoadjuvant chemotherapy administered for locally advanced tumors, including those in breast cancer, demonstrated therapy could induce sufficient tumor regression to allow for the resection of otherwise unresectable tumors. Subsequent demonstration of the equivalence of lumpectomy to mastectomy in patients with operable breast cancer, stimulated interest in the concept of using preoperative chemotherapy to reduce large, but operable, primary tumors to allow for lumpectomy in women who would otherwise require a mastectomy. Given the data from previous studies, it is appropriate to continue development of sequential doxorubicin/cyclophosphamide/docetaxel regimens to improve on clinical and pathologic response rates. FB-4 is a Phase II, single arm study for women with locally advanced human epidermal growth factor receptor 2 (HER2)-negative breast cancer diagnosed by core needle biopsy. The primary aim of the study is to determine the pathologic complete response rate in the breast following neoadjuvant chemotherapy combined with bevacizumab.

Conditions
Breast Cancer
Keywords
NSABP, Doxorubicin, Cyclophosphamide, Bevacizumab, Capecitabine, Docetaxel, Breast cancer, Locally advanced, Neoadjuvant, Locally advanced breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabDrug

    Also called Avastin

    15 mg/kg IV every 21 days x 4 cycles, then after clinical response assessment, 15 mg/kg IV every 21 days x 2 cycles, then following surgery, 15 mg/kg every 21 days x 10 cycles

  • DoxorubicinDrug

    60 mg/m^2 IV every 21 days x 4 cycles

  • CyclophosphamideDrug

    600 mg/m^2 IV every 21 days x 4 cycles

  • CapecitabineDrug

    Also called Xeloda

    Following clinical response assessment, 650 mg/m^2 twice a day (orally), days 1-14 every 21 days x 4 cycles

  • DocetaxelDrug

    Also called Taxotere

    Following clinical response assessment, 75 mg/m^2 IV every 21 days x 4 cycles

Study groups in NCT00365417
Study groupRoleWhat they receive
Doxorubicin+Cyclophosphamide+BevacizumabExperimentalNot described
Receives: Drug: Bevacizumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Capecitabine; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic Complete Response (pCR) in the Breast

    Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen

    Measured: Approximately 7 months

Secondary outcomes (7)

  1. pCR in the Breast and Nodes

    Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel nodes

    Measured: Approximately 7 months

  2. Clinical Response Rate (cRR) of the Sequential Regimen

    Clinical tumor measurements were required before study entry \& before cycle 5 of chemotherapy (between AC \& TX). Final tumor measurements were obtained 4-5 weeks after the last dose of chemotherapy. Clinical tumor assessments by physical examination were recommended before each chemotherapy cycle. The criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee(RECIST) were used to define clinical response status. CR was defined as the disappearance of all lesions with no evidence of PD. PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions, using as reference the baseline sum longest diameter and/or the persistence of greater than or equal to 1 nontarget lesion without worsening of any other clinical manifestations of disease. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions, or unequivocal progression of existing lesions.

    Measured: Approximately 6 months

  3. Reported Adverse Events

    Number of Adverse Events

    Measured: Approximately 14 months

  4. Cardiac Events

    Events: Congestive Heart Failure; Cardiac Death

    Measured: Assessments throughout; up to 18 months following study entry

  5. Progression-free Survival

    Percentage of patients free from disease progression. Progression is determined using international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. At least a 20% increase in the sum of the longest diameter of the target lesions. Other manifestations of progressive disease would also be classified as disease progression, eg., appearance of one or more new lesions in the breast, regional lymph nodes or distant sites, unequivocal progression of existing non-target lesions, and appearance of inflammatory carcinoma on clinical exam.

    Measured: 2 years

  6. Overall Survival

    Percentage of patients alive.

    Measured: 2 years

  7. Number of Patients With at Least One Surgical Complications (Wound Dehiscence, Infection, Seroma, or Hematoma).

    Number of patients with at least one surgical complications (wound dehiscence, infection, seroma, or hematoma)

    Measured: Two (2) years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Aug 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionFeb 2008
  4. Study completionNov 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00365417
Sponsor's protocol ID
NSABP FB-4
Status last verified
Mar 2020
First submitted
15 Aug 2006
Last updated
13 Apr 2021
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Doxorubicin and Cyclophosphamide in people with Breast Cancer, run by NSABP Foundation Inc at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Complete Response (pCR) in the Breast (time frame: Approximately 7 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00365417.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2021.

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Clinical Trial NCT00365417 | AzTrials