Know Cancer

forgot password

Phase II Feasibility Trial Incorporating Bevacizumab Into Dose Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Patients With Lymph Node Positive Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

Phase II Feasibility Trial Incorporating Bevacizumab Into Dose Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Patients With Lymph Node Positive Breast Cancer


I. Determine the incidence of clinically apparent cardiac dysfunction in patients with
resected lymph node-positive breast cancer treated with adjuvant bevacizumab and dose dense
doxorubicin and cyclophosphamide followed by paclitaxel.


I. Determine the changes in left ventricular ejection fraction (LVEF) in patients treated
with this regimen.

II. Determine the non-cardiac toxicity of this regimen in these patients.

OUTLINE: This is a non-randomized, multicenter study. Patients are sequentially assigned to
1 of 2 treatment arms.

ARM A: Patients receive doxorubicin IV, cyclophosphamide IV over 20-30 minutes, and
bevacizumab IV over 30-90 minutes on day 1. Patients also receive filgrastim (G-CSF)
subcutaneously (SQ) on days 2-11 or pegfilgrastim SC on day 2. Treatment repeats every 14
days for 4 courses. Patients then receive paclitaxel IV over 3 hours and bevacizumab IV over
30-90 minutes on day 1. Patients also receive G-CSF or pegfilgrastim as above. Treatment
with paclitaxel, bevacizumab, and G-CSF or pegfilgrastim repeats every 14 days for 4
courses. Patients then receive bevacizumab alone every 14 days for up to 18 courses.

ARM B: Patients receive doxorubicin, cyclophosphamide, and G-CSF or pegfilgrastim as in
group I. Patients then receive paclitaxel, bevacizumab, and G-CSF or pegfilgrastim as in
group I. Patients then receive bevacizumab alone every 14 days for up to 22 courses.

Treatment in both groups continues in the absence of disease recurrence or unacceptable

Patients who require radiotherapy (post-lumpectomy) or who plan radiotherapy at the
discretion of the investigator (post-mastectomy) undergo radiotherapy beginning within 6
weeks after the completion of chemotherapy.

Premenopausal patients with estrogen receptor (ER) and / or progesterone receptor (PR)
positive disease receive oral tamoxifen once daily for 5 years beginning at the time of
radiotherapy or within 6 weeks after the completion of chemotherapy. Postmenopausal patients
with ER and / or PR positive disease receive an aromatase inhibitor (e.g., anastrozole,
letrozole, or exemestane) or tamoxifen followed by an aromatase inhibitor once daily for up
to 10 years.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for up to 3 years from study entry.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the breast

- Node-positive disease in 1 or more axillary or internal mammary lymph node by
histology with hematoxylin and eosin staining

- Has undergone prior definitive breast surgery including total mastectomy and axillary
dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy,
lumpectomy and axillary dissection or lumpectomy and sentinel node biopsy within the
past 29-84 days (arm A only)

- Surgical margins must be histologically free of invasive tumor and ductal
carcinoma in situ, but lobular carcinoma in situ allowed

- Synchronous bilateral breast cancer diagnosed within the past month allowed provided
the higher TNM (Tumor,Node,Metastasis) stage tumor meets study eligibility criteria

- Age>=18

- ECOG performance status of 0-2

- Adequate organ function as evidenced by following, obtained within 8 weeks prior to

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 1.5 mg/dL

- Aspartate aminotransferase (AST) ≤ 2 times upper limit normal (ULN)

- Prothrombin time international normalized ratio (PT INR) ≤ 1.5 times normal

- Partial thromboplastin time (PTT) ≤ 1.5 times normal

- Creatinine ≤ 1.5 mg/dL

- Urine protein:creatinine ratio < 1.0

- Left ventricular ejection fraction (LVEF) normal by multi gated acquisition scan
(MUGA) or echocardiogram (ECHO)

- Fertile patients must use effective contraception during and for 3-4 months after
completion of study treatment

- Prior tamoxifen or raloxifene for chemoprevention allowed

- More than 4 weeks since prior major surgery

- Non-operative biopsy or placement of a vascular access device is not considered
major surgery

- Regular use of cyclo-oxygenase-2 inhibitors or low-dose aspirin allowed

Exclusion Criteria:

- With immunohistologic staining as the only evidence of nodal involvement

- Her2/neu-positive disease(i.e.,3+ by immunohistochemistry or positive by fluorescent
in situ hybridization)

- Clinical evidence of inflammatory disease or fixed axillary nodes (N2)

- History of myocardial infarction within the past year

- History of unstable angina within the past year

- History of arterial thrombotic events within the past year

- Uncontrolled or clinically significant arrhythmia

- New York Heart Association grade II-IV congestive heart failure

- Peripheral vascular disease ≥ grade II

- Uncontrolled hypertension, defined as systolic blood pressure (BP)>160 mm Hg or
diastolic BP>90 mm Hg

- History of deep venous thrombosis

- History of cerebrovascular disease, including transient ischemic attack or stroke

- Other clinically significant cardiovascular disease

- History of pulmonary embolism

- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- Non-healing wound or bone fracture

- Hypersensitivity to paclitaxel or drugs using Cremophor

- Hypersensitivity to Chinese hamster ovary cell products or other recombinant human

- Pregnant

- Nursing during and for ≥ 3-4 months after completion of study treatment

- Prior cytotoxic chemotherapy for breast cancer

- Prior anthracycline, anthracenedione, or taxane for any condition

- Prior hormonal therapy for breast cancer

- Other concurrent tamoxifen or raloxifene

- Prior radiotherapy for breast cancer

- Concurrent radiotherapy to the internal mammary chain

- Concurrent therapeutic anticoagulants

- Concurrent prophylactic use of anticoagulants to maintain patency of vascular
assess device allowed

- Concurrent regular use of aspirin (i.e., daily for ≥ 10 days at doses of > 325
mg/day) or regular therapeutic doses of other nonsteroidal anti-inflammatory drugs
known to inhibit platelet function

- Other concurrent drugs known to inhibit platelet function, including any of the

- Dipyridamole

- Ticlopidine

- Clopidogrel

- Cilostazol

- Concurrent cardioprotectant agents

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Congestive Heart Failure Rate

Outcome Description:

Clinical congestive heart failure includes patients with symptomatic decline in LVEF to at or below the lower limit of normal (LLN), or symptomatic diastolic dysfunction. 223 treated patients were included in the analysis.

Outcome Time Frame:

assessed on day 1 of cycles 5, 9, 17 and 25, and at end of treatment, then every 3 months for <2 years and every 6 months for 2-3 years from study entry

Safety Issue:


Principal Investigator

Kathy Miller, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Indiana University Melvin and Bren Simon Cancer Center


United States: Federal Government

Study ID:




Start Date:

October 2005

Completion Date:

September 2009

Related Keywords:

  • Breast Cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • male breast cancer
  • lymph node positive breast cancer
  • Breast Neoplasms



George Washington University Medical Center Washington, District of Columbia  20037
Mayo Clinic - Jacksonville Jacksonville, Florida  32224
Mayo Clinic Cancer Center Rochester, Minnesota  55905
Indiana University Cancer Center Indianapolis, Indiana  46202-5265
CCOP - Wichita Wichita, Kansas  67214-3882
Hurley Medical Center Flint, Michigan  48503
CCOP - Missouri Valley Cancer Consortium Omaha, Nebraska  68131
CCOP - Carle Cancer Center Urbana, Illinois  61801
CCOP - Iowa Oncology Research Association Des Moines, Iowa  50309-1016
Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Aurora Presbyterian Hospital Aurora, Colorado  80012
Boulder Community Hospital Boulder, Colorado  80301-9019
Penrose Cancer Center at Penrose Hospital Colorado Springs, Colorado  80933
Porter Adventist Hospital Denver, Colorado  80210
Presbyterian - St. Luke's Medical Center Denver, Colorado  80218
St. Joseph Hospital Denver, Colorado  80218
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center Grand Junction, Colorado  81502
Sky Ridge Medical Center Lone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United Hospital Longmont, Colorado  80502
North Suburban Medical Center Thornton, Colorado  80229
Rush-Copley Cancer Care Center Aurora, Illinois  60507
Evanston Northwestern Healthcare - Evanston Hospital Evanston, Illinois  60201-1781
Hinsdale Hematology Oncology Associates Hinsdale, Illinois  60521
Joliet Oncology-Hematology Associates, Limited - West Joliet, Illinois  60435
Carle Cancer Center at Carle Foundation Hospital Urbana, Illinois  61801
Saint Anthony Memorial Health Centers Michigan City, Indiana  46360
Cedar Rapids Oncology Associates Cedar Rapids, Iowa  52403
Mercy Medical Center - Sioux City Sioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLP Sioux City, Iowa  51101
St. Luke's Regional Medical Center Sioux City, Iowa  51104
CCOP - Michigan Cancer Research Consortium Ann Arbor, Michigan  48106
Oakwood Cancer Center at Oakwood Hospital and Medical Center Dearborn, Michigan  48123-2500
Genesys Hurley Cancer Institute Flint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods, Michigan  48236
Foote Hospital Jackson, Michigan  49201
Bronson Methodist Hospital Kalamazoo, Michigan  49007
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Borgess Medical Center Kalamazooaa, Michigan  49001
Sparrow Regional Cancer Center Lansing, Michigan  48912-1811
Seton Cancer Institute - Saginaw Saginaw, Michigan  48601
St. John Macomb Hospital Warren, Michigan  48093
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Hutchinson Area Health Care Hutchinson, Minnesota  55350
Meeker County Memorial Hospital Lichfield, Minnesota  55355
HealthEast Cancer Care at St. John's Hospital Maplewood, Minnesota  55109
Hennepin County Medical Center - Minneapolis Minneapolis, Minnesota  55415
Regions Hospital Cancer Care Center St. Paul, Minnesota  55101
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Minnesota Oncology Hematology, PA - Woodbury Woodbury, Minnesota  55125
CCOP - MeritCare Hospital Fargo, North Dakota  58122
Mercy Cancer Center at Mercy Medical Center Canton, Ohio  44708
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
St. Rita's Medical Center Lima, Ohio  45801
Natalie Warren Bryant Cancer Center at St. Francis Hospital Tulsa, Oklahoma  74136
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Penn State Cancer Institute at Milton S. Hershey Medical Center Hershey, Pennsylvania  17033-0850
Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283
Geisinger Medical Group - Scenery Park State College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre, Pennsylvania  18711
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Marshfield Clinic - Marshfield Center Marshfield, Wisconsin  54449
University of Alabama at Birmingham Comprehensive Cancer Center Birmingham, Alabama  35294-3300
Memorial Hospital of South Bend South Bend, Indiana  46601
Reading Hospital and Medical Center Reading, Pennsylvania  19612-6052
Mercy Hospital Cancer Center - Scranton Scranton, Pennsylvania  18501
CCOP - MainLine Health Wynnewood, Pennsylvania  19096
University of Miami Sylvester Comprehensive Cancer Center Miami, Florida  33136
Hinsdale, Illinois  60521
CCOP - Northern Indiana CR Consortium South Bend, Indiana  46601
Saint Joseph Regional Medical Center South Bend, Indiana  46617
Siteman Cancer Center at Barnes-Jewish Hospital Saint Louis, Missouri  63110
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines, Iowa  50309
St. Vincent Mercy Medical Center Toledo, Ohio  43608
CCOP - Colorado Cancer Research Program, Incorporated Denver, Colorado  80224
Overlook Hospital Summit, New Jersey  07902-0220
Washington Cancer Institute at Washington Hospital Center Washington, District of Columbia  20010
Carol G. Simon Cancer Center at Morristown Memorial Hospital Morristown, New Jersey  07962
Cancer Institute of New Jersey at Hamilton Hamilton, New Jersey  08690
CCOP - Toledo Community Hospital Toledo, Ohio  43623-3456
Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando, Florida  32803-1273
Via Christi Cancer Center at Via Christi Regional Medical Center Wichita, Kansas  67214
Albert Einstein Cancer Center at Albert Einstein College of Medicine Bronx, New York  10461
NYU Cancer Institute at New York University Medical Center New York, New York  10016
Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina  27157-1096
Medical University of Ohio Cancer Center Toledo, Ohio  43614
Toledo Hospital Toledo, Ohio  43606
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
Aultman Hospital Cancer Center at Aultman Health Foundation Canton, Ohio  44710-1799
Green Bay Oncology, Limited - Escanaba Escanaba, Michigan  49431
Hunterdon Regional Cancer Center at Hunterdon Medical Center Flemington, New Jersey  08822
CCOP - Hematology-Oncology Associates of Central New York East Syracuse, New York  13057
Lewistown Hospital Lewistown, Pennsylvania  17044
Mount Nittany Medical Center State College, Pennsylvania  16803
St. Mary's Hospital Medical Center - Green Bay Green Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Mary's Hospital Green Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical Center Marinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto Falls Oconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon Bay Sturgeon Bay, Wisconsin  54235
Hematology Oncology Associates of the Quad Cities Bettendorf, Iowa  52722
Baptist Cancer Institute - Jacksonville Jacksonville, Florida  32207
Siouxland Regional Cancer Center Sioux City, Iowa  51101-1733
Southwest Medical Center Liberal, Kansas  67901
Wayne Memorial Hospital, Incorporated Goldsboro, North Carolina  27534
New Hampshire Oncology-Hematology, PA - Hooksett Hooksett, New Hampshire  03106
Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph Saint Joseph, Michigan  49085
Lenoir Memorial Cancer Center Kinston, North Carolina  28503-1678
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center Washington, District of Columbia  20007
Swedish-American Regional Cancer Center Rockford, Illinois  61104-2315
St. Barnabas Medical Center Cancer Center Livingston, New Jersey  07039
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick, New Jersey  08903
Elkhart General Hospital Elkhart, Indiana  46515
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton Marlton, New Jersey  08053
Fox Chase Virtua Health Cancer Program at Virtua West Jersey Voorhees, New Jersey  08043
Fox Chase Cancer Center - Philadelphia Philadelphia, Pennsylvania  19111-2497
Front Range Cancer Specialists Fort Collins, Colorado  80528
Joan Karnell Cancer Center at Pennsylvania Hospital Philadelphia, Pennsylvania  19107
Memorial Medical Center Cancer Services Modesto, California  95355
St. Mary-Corwin Regional Medical Center Pueblo, Colorado  81004
Ingalls Cancer Care Center at Ingalls Memorial Hospital Harvey, Illinois  60426
Trinity Medical Center - East Moline, Illinois  61265
Fort Wayne Medical Oncology and Hematology Fort Wayne, Indiana  46815
Howard Community Hospital at Howard Regional Health System Kokomo, Indiana  46904
Center for Cancer Therapy at LaPorte Hospital and Health Services La Porte, Indiana  46350
Bettendorf, Iowa  52722
John Stoddard Cancer Center at Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
Mercy Capitol Hospital Des Moines, Iowa  50307
Medical Oncology and Hematology Associates at John Stoddard Cancer Center Des Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer Center Des Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des Moines West Des Moines, Iowa  50266
Cancer Center of Kansas, PA - Dodge City Dodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical Center Adrian, Michigan  49221
St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital Ann Arbor, Michigan  48106-0995
Green Bay Oncology, Limited - Iron Mountain Iron Mountain, Michigan  49801
Community Cancer Center of Monroe Monroe, Michigan  48162
Mercy Memorial Hospital System Monroe, Michigan  48162
MeritCare Clinic - Bemidji Bemidji, Minnesota  56601
Virginia Piper Cancer Institute at Abbott-Northwestern Hospital Minneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Medical Center Robbinsdale, Minnesota  55422-2900
Park Nicollet Health Services St. Louis Park, Minnesota  55416
Immanuel Medical Center Omaha, Nebraska  68122
Creighton University Medical Center Omaha, Nebraska  68131-2197
Mountainside Hospital Cancer Center Montclair, New Jersey  07042
Booker Cancer Center at Riverview Medical Center Red Bank, New Jersey  07701
Iredell Memorial Hospital Statesville, North Carolina  28677
MeritCare Medical Group Fargo, North Dakota  58122
Wood County Oncology Center Bowling Green, Ohio  43402
Blanchard Valley Medical Associates Findlay, Ohio  45840
Fremont Memorial Hospital Fremont, Ohio  43420
Kenton Oncology, Incorporated Kenton, Ohio  43326
Lima Memorial Hospital Lima, Ohio  45804
St. Luke's Hospital Maumee, Ohio  43537
Northwest Ohio Oncology Center Maumee, Ohio  43537
Toledo Clinic - Oregon Oregon, Ohio  43616
St. Charles Mercy Hospital Oregon, Ohio  43616
North Coast Cancer Care, Incorporated Sandusky, Ohio  44870
Firelands Regional Medical Center Sandusky, Ohio  44870
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Toledo Clinic, Incorporated - Main Clinic Toledo, Ohio  43623
Fulton County Health Center Wauseon, Ohio  43567
Bryn Mawr Hospital Bryn Mawr, Pennsylvania  19010
St. Mary Regional Cancer Center Langhorne, Pennsylvania  19047
Hematology and Oncology Associates Scranton, Pennsylvania  18510
Lankenau Cancer Center at Lankenau Hospital Wynnewood, Pennsylvania  19096
Baptist Regional Cancer Center at Baptist Hospital of East Tennessee Knoxville, Tennessee  37901
Green Bay Oncology, Limited at St. Vincent Hospital Green Bay, Wisconsin  54301-3526
DeCesaris Cancer Institute at Anne Arundel Medical Center Annapolis, Maryland  21401
Morton Hospital & Medical Center Taunton, Massachusetts  02780
Cancer Care Center at St. Luke's Hospital Duluth, Minnesota  55805
Saint Francis Cancer Center Shakopee, Minnesota  55379
St. Joseph's Hospital St Paul, Minnesota  55102
Carl and Dorothy Bennett Cancer Center at Stamford Hospital Stamford, Connecticut  06904
William N. Wishard Memorial Hospital Indianapolis, Indiana  46202
McFarland Clinic, PC Ames, Iowa  50010
Cancer Center of Kansas, PA - Chanute Chanute, Kansas  66720
Cancer Center of Kansas, PA - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas, PA - Kingman Kingman, Kansas  67068
Cancer Center of Kansas, PA - Newton Newton, Kansas  67114
Cancer Center of Kansas, PA - Parsons Parsons, Kansas  67357
Cancer Center of Kansas, PA - Pratt Pratt, Kansas  67124
Cancer Center of Kansas, PA - Salina Salina, Kansas  67401
Cancer Center of Kansas, PA - Wellington Wellington, Kansas  67152
Cancer Center of Kansas, PA - Wichita Wichita, Kansas  67214
Associates in Womens Health, PA - North Review Wichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas, PA - Winfield Winfield, Kansas  67156
Haematology-Oncology Associates of Ohio and Michigan, PC Lambertville, Michigan  48144
Willmar Cancer Center at Rice Memorial Hospital Willmar, Minnesota  56201
Alegant Health Cancer Center at Bergan Mercy Medical Center Omaha, Nebraska  68124
Flower Hospital Cancer Center Sylvania, Ohio  43560
Ministry Medical Group at Saint Mary's Hospital Rhinelander, Wisconsin  54501
Methodist Cancer Center at Methodist Hospital - Omaha Omaha, Nebraska  68114
Stanford Comprehensive Cancer Center at Stanford University Medical Center Stanford, California  94305
Elliot Regional Cancer Center at Elliot Hospital Manchester, New Hampshire  03103
Manchester Memorial Hospital Manchester, Connecticut  06040-4188
Sherman Hospital Elgin, Illinois  60120-2198
Oncology/Hematology Associates of Southwest Indiana at St. Mary's Cancer Center Evansville, Indiana  47714
Woodwinds Health Campus Woodbury, Minnesota  55125
Cancer Center of Paoli Memorial Hospital Paoli, Pennsylvania  19301-1792
Minnesota Oncology Hematology, PA at Maplewood Cancer Center Maplewood, Minnesota  55109
Community Hospital of the Monterey Peninsula Comprehensive Cancer Center Monterey, California  93940
Arnett Cancer Care Lafayette, Indiana  47904
Bendheim Cancer Center at Greenwich Hospital Greenwich, Connecticut  06830
Norwalk Hospital Norwalk, Connecticut  06856
York Hospital York, Maine  03909
Cancer Center at Erlanger Health Chattanooga, Tennessee  37403