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Chemotherapy With or Without Bevacizumab in Treating Women With Stage I, Stage II, or Stage IIIA Breast Cancer That Can Be Removed By Surgery
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
Sponsors and Collaborators: National Surgical Adjuvant Breast and Bowel Project (NSABP)
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00408408
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy and bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known which chemotherapy regimen is more effective with or without bevacizumab in treating breast cancer.

PURPOSE: This randomized phase III trial is studying six different chemotherapy regimens to compare how well they work with or without bevacizumab in treating women with stage I, stage II, or stage IIIA breast cancer that can be removed by surgery.


Condition Intervention Phase
Breast Cancer
Drug: bevacizumab
Drug: capecitabine
Drug: cyclophosphamide
Drug: docetaxel
Drug: doxorubicin hydrochloride
Drug: gemcitabine hydrochloride
Procedure: conventional surgery
Phase III

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Docetaxel Gemcitabine hydrochloride Gemcitabine Capecitabine Bevacizumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: A Randomized Phase III Trial of Neoadjuvant Therapy in Patients With Palpable and Operable Breast Cancer Evaluating the Effect on Pathologic Complete Response (pCR) of Adding Capecitabine or Gemcitabine to Docetaxel When Administered Before AC With or Without Bevacizumab and Correlative Science Studies Attempting to Identify Predictors of High Likelihood for pCR With Each of the Regimens

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Pathologic complete response (pCR) of the primary tumor in the breast [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • pCR in the breast and nodes [ Designated as safety issue: No ]
  • Clinical overall response (cOR) following docetaxel alone, docetaxel/capecitabine, and docetaxel/gemcitabine hydrochloride, with or without bevacizumab, as assessed by physical exam at the completion of the docetaxel-based portion of chemotherapy [ Designated as safety issue: No ]
  • cOR as assessed by physical exam at the completion of the sequential chemotherapy regimens [ Designated as safety issue: No ]
  • Clinical complete response (cCR) following docetaxel alone, docetaxel/capecitabine, and docetaxel/gemcitabine hydrochloride, with or without bevacizumab, as assessed by physical exam at completion of therapy [ Designated as safety issue: No ]
  • cCR as assessed by physical exam at the completion of the sequential chemotherapy regimens [ Designated as safety issue: No ]
  • Percentage of cardiac events [ Designated as safety issue: No ]
  • Percentage of surgical complications [ Designated as safety issue: No ]
  • Toxicities [ Designated as safety issue: Yes ]
  • Disease-free survival [ Designated as safety issue: No ]
  • Incidence of recurrence after mastectomy [ Designated as safety issue: No ]
  • Incidence of local recurrence in the ipsilateral breast following lumpectomy [ Designated as safety issue: No ]
  • Incidence of regional recurrence [ Designated as safety issue: No ]
  • Incidence of distant recurrence [ Designated as safety issue: No ]
  • Incidence of contralateral breast cancer [ Designated as safety issue: No ]
  • Incidence of second primary cancer [ Designated as safety issue: No ]
  • Mortality from any cause prior to recurrence or second primary cancer [ Designated as safety issue: No ]

Estimated Enrollment: 1200
Study Start Date: November 2006
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator
Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive AC comprising doxorubicin hydrochloride IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses. Patients then undergo surgery (lumpectomy or mastectomy).
Drug: bevacizumab
Given IV
Drug: cyclophosphamide
Given IV
Drug: docetaxel
Given IV
Drug: doxorubicin hydrochloride
Given IV
Procedure: conventional surgery
Patients undergo surgery
Arm II: Experimental
Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel as in Arm I. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive AC as in Arm I and 2 additional courses of bevacizumab concurrent with the first 2 courses of AC. Patients then undergo surgery as in Arm I. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.
Drug: cyclophosphamide
Given IV
Drug: docetaxel
Given IV
Drug: doxorubicin hydrochloride
Given IV
Procedure: conventional surgery
Patients undergo surgery
Arm III: Experimental
Patients receive docetaxel as in Arm I and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive AC as in Arm I. Patients then undergo surgery as in Arm I.
Drug: capecitabine
Given orally
Drug: cyclophosphamide
Given IV
Drug: docetaxel
Given IV
Drug: doxorubicin hydrochloride
Given IV
Procedure: conventional surgery
Patients undergo surgery
Arm IV: Experimental
Patients receive bevacizumab as in Arm II and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive bevacizumab IV over 30 minutes on day 1 and AC as in Arm I. Treatment repeats every 3 weeks for up to 4 courses (2 courses of bevacizumab). Patients then undergo surgery as in Arm I. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm II.
Drug: bevacizumab
Given IV
Drug: capecitabine
Given orally
Drug: cyclophosphamide
Given IV
Drug: docetaxel
Given IV
Drug: doxorubicin hydrochloride
Given IV
Procedure: conventional surgery
Patients undergo surgery
Arm V: Experimental
Patients receive docetaxel as in Arm I and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive AC as in Arm I. Patients then undergo surgery as in Arm I.
Drug: cyclophosphamide
Given IV
Drug: docetaxel
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: gemcitabine hydrochloride
Given IV
Procedure: conventional surgery
Patients undergo surgery
Arm VI: Experimental
Patients receive docetaxel as in Arm I, gemcitabine hydrochloride as in Arm V, and bevacizumab as in Arm II. Patients then receive AC with bevacizumab as in Arm II. Patients then undergo surgery as in Arm I. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm II.
Drug: bevacizumab
Given IV
Drug: cyclophosphamide
Given IV
Drug: docetaxel
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: gemcitabine hydrochloride
Given IV
Procedure: conventional surgery
Patients undergo surgery

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive adenocarcinoma of the breast

    • Primary breast tumor must be palpable and measure ≥ 2.0 cm on physical exam
    • No stage T4 disease
    • No ipsilateral cN2b or cN3 disease

      • cN1 or cN2a disease allowed
    • Histology confirmed by core-needle biopsy
  • No prior surgical axillary staging procedure

    • Fine-needle aspiration or core biopsy of an axillary node allowed
    • Pre-neoadjuvant therapy sentinel lymph node biopsy allowed if axillary nodes clinically negative
  • HER2-negative disease by immunohistochemistry (< 3+) or by fluorescent in situ hybridization (negative for gene amplification)
  • No prior excisional or incisional biopsy for primary breast tumor
  • No synchronous bilateral breast cancer (invasive or ductal carcinoma in situ [DCIS])
  • No prior breast cancer, including DCIS

    • Prior lobular carcinoma in situ allowed
  • No clinical or radiologic evidence of metastatic disease
  • Hormone receptor status known

PATIENT CHARACTERISTICS:

  • Female
  • Menopausal status not specified
  • ECOG performance status 0-1
  • Not pregnant or nursing
  • Negative pregnancy test
  • LVEF ≥ the lower limit of normal or ≥ 50% by MUGA or echocardiogram within the past 3 months
  • Absolute neutrophil count ≥ 1,200/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL
  • Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
  • AST ≤ 1.5 times ULN

    • Alkaline phosphatase and AST must not both be > ULN
    • Patients with either skeletal pain or alkaline phosphatase that is > ULN but ≤ 2.5 times ULN are allowed if bone scans do not demonstrate metastatic disease
    • AST or alkaline phosphatase > ULN allowed if liver imaging does not demonstrate metastatic disease
  • Bilirubin normal (≤ 1.5 times ULN for Gilbert's disease or similar syndrome)
  • Serum creatinine ≤ ULN
  • Creatinine clearance > 50 mL/min
  • Urine protein:urine creatinine ratio < 1.0
  • Able to swallow oral medications
  • No other malignancies except carcinoma in situ of the cervix or colon, melanoma in situ, or basal cell or squamous cell carcinoma of the skin, unless the patient is considered to be disease-free for the past 5 years and at low-risk for recurrence
  • No cardiovascular-related condition that would preclude the use of anthracyclines, including any of the following:

    • Angina pectoris that requires the use of antianginal medication
    • History of documented congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Severe conduction abnormality
    • Valvular disease with documented cardiac function compromise
    • Uncontrolled hypertension, defined as blood pressure > 150/90 mm Hg on antihypertensive therapy

      • Hypertension well controlled with medication allowed
  • No history of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular function
  • No history of transient ischemic attack or cerebrovascular accident
  • No arterial thrombotic event within the past 12 months
  • No symptomatic peripheral vascular disease
  • No significant nontraumatic bleeding within the past 6 months
  • No significant traumatic injury within the past 28 days
  • No serious or nonhealing wound, skin ulcers, or incompletely healed bone fracture
  • No active (by endoscopy) gastroduodenal ulcer(s)
  • No known bleeding diathesis or coagulopathy

    • Patients on warfarin with an in-range INR (between 2 and 3) allowed
  • No sensory or motor neuropathy ≥ grade 2
  • No conditions that would prohibit administration of corticosteroids
  • No history of severe hypersensitivity reaction to drugs formulated with polysorbate 80
  • No other nonmalignant systemic disease that would preclude study treatment or prevent required follow-up

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior radiation therapy, chemotherapy, biologic therapy, and/or hormonal therapy for the currently diagnosed breast cancer
  • No prior anthracyclines, taxanes, capecitabine, fluorouracil, gemcitabine hydrochloride, or bevacizumab for any malignancy
  • No investigational agents within the past 30 days
  • No major surgical procedure or open biopsy within the past 28 days

    • Placement of a vascular access device is not considered a major surgical procedure
  • No concurrent sex hormone therapy (e.g., birth control pills, ovarian hormone replacement therapy)
  • No concurrent hormonal agent, such as raloxifene, tamoxifen, or other selective estrogen-receptor modulator (SERM), either for osteoporosis or breast cancer prevention
  • No major surgical procedures (other than the required breast surgery) during the course of the study
  • No other concurrent anticancer therapy
  • No concurrent partial breast radiation therapy and brachytherapy
  • No concurrent participation in other clinical trials employing an investigational agent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00408408

  Show 394 Study Locations
Sponsors and Collaborators
National Surgical Adjuvant Breast and Bowel Project (NSABP)
Investigators
Study Chair: Harry D. Bear, MD, PhD Massey Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000515432, NSABP-B-40
Study First Received: December 6, 2006
Last Updated: January 15, 2009
ClinicalTrials.gov Identifier: NCT00408408  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

Study placed in the following topic categories:
Docetaxel
Capecitabine
Skin Diseases
Breast Neoplasms
Bevacizumab
Cyclophosphamide
Gemcitabine
Doxorubicin
Breast Diseases

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Angiogenesis Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses
Myeloablative Agonists
Growth Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009