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A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab or Placebo in Patients With Lymph Node Positive and High Risk Lymph Node Negative Breast Canc

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Trial Conditions
  • Breast Cancer
  • Estrogen Receptor-negative Breast Cancer
  • Estrogen Receptor Negative
  • Estrogen Receptor Positive
  • Estrogen Receptor-positive Breast Cancer
  • HER2-negative Breast Cancer
  • HER2/Neu Negative
  • Male Breast Carcinoma
  • Stage II Breast Cancer
  • Male Breast Cancer
  • Stage IA Breast Cancer
  • Stage IB Breast Cancer
  • Stage IIA Breast Cancer
  • Stage IIB Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
What is the purpose of this trial?

This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with cancer that has spread to the lymph nodes (lymph node-positive) or cancer that has not spread to the lymph nodes but is at high risk for returning (high-risk, lymph node-negative breast cancer). Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery and help prevent the tumor from returning. It is not yet known whether doxorubicin hydrochloride, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab.

Date & Status

Active, not recruiting

Who can Participate?

Eligibility

Ages:
18 and older

Gender:
Both

Eligibility

Inclusion Criteria:

- Patients must have histologically confirmed adenocarcinoma of the breast at
significant risk of distant recurrence based on at least one of the following
criteria:

- For axillary lymph node positive disease:

- Involvement of at least one sentinel or axillary lymph node on routine
histologic examination; patients with negative sentinel nodes and negative
axillary nodes or involvement only demonstrated by immunohistochemistry are
not eligible unless they meet one of the other eligibility criteria below

- NOTE: consider intramammary nodes as equivalent to axillary nodes for the
purposes of eligibility and stratification

- For axillary lymph node negative disease:

- Estrogen receptor (ER) negative tumor >= 1 cm

- ER+ tumor >= 5 cm regardless of recurrence score

- ER+ tumor >= 1 cm but < 5 cm with a recurrence score >= 11 (patients
enrolled in the TAILORx trial are eligible)

- NOTE: axillary dissection is strongly encouraged in patients with lymph
node involvement identified on sentinel node biopsy

- Patients must have completed definitive breast surgery including total mastectomy and
axillary dissection (modified radical mastectomy), total mastectomy and sentinel node
biopsy, breast conservation surgery and axillary dissection or breast conservation
surgery and sentinel node biopsy

- NOTE: breast conservation surgery includes lumpectomy, partial mastectomy, and
excisional biopsy

- Margins of breast conservation surgery or mastectomy must be histologically free of
invasive breast cancer and ductal carcinoma in situ (DCIS); patients with resection
margins positive for lobular carcinoma in situ (LCIS) are eligible

- Time from last surgery for breast cancer (breast conservation surgery, mastectomy,
sentinel node biopsy, axillary dissection or re-excision of breast conservation
surgery margins) to planned treatment start date must be > 28 days and =< 84 days

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Absolute neutrophil count >= 1,000/mm^3

- Platelet count >= 100,000/mm^3

- Total bilirubin =< 1.5 mg/dL

- Aspartate aminotransferase (AST) =< 2 times upper limit of normal(ULN)

- Serum creatinine =< 1.5 mg/dL

- Urine protein:creatinine ratio < 1.0 or 24-hour protein

- Partial thromboplastin time (PTT) =< 1.5 times ULN

- Left ventricle ejection fraction (LVEF) >= institutional limits of normal by
echocardiogram (ECHO) or multigated acquisition scan (MUGA)

- Patients who have undergone breast conservation surgery must receive radiation; prior
to randomization, the investigator must specify the planned radiation technique:

- Whole breast radiation (WBRT) after chemotherapy

- Accelerated partial breast radiation (APBI) after chemotherapy

- Accelerated partial breast radiation (APBI) prior to chemotherapy

- NOTE: if APBI was completed prior to study entry, day 1 of protocol therapy must
be at least 4 weeks after the completion of APBI

- Post-mastectomy radiation therapy (RT) is required for all patients with a primary
tumor of >= 5 cm or involvement of 4 or more lymph nodes; post-mastectomy RT may be
administered at the investigator's discretion for all other mastectomy patients

- Patients with human epidermal growth factor receptor (HER)2 + (3+ by
immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] ratio >= 2)
breast cancer are not eligible

- Patients with synchronous bilateral breast cancer (diagnosed within one month) are
eligible if the higher tumor, node, metastasis (TNM) stage tumor meets the
eligibility criteria for this trial

- Patients must not have clinical evidence of inflammatory disease or fixed axillary
nodes at diagnosis

- Patients must not have received prior cytotoxic chemotherapy or hormonal therapy for
this breast cancer; prior treatment with an anthracycline, anthracenedione or taxane
for any condition is not allowed

- NOTE: prior use of tamoxifen for chemoprevention is allowed but must be
discontinued at study entry; similarly, prior raloxifene use is allowed but must
be discontinued at study entry

- Patients must not have had any major surgical procedure within 28 days of planned
treatment start date

- NOTE: non-operative biopsy or placement of a vascular access device is not
considered a major surgery

- Patients may not have had placement of a vascular access device within 24 hours of
planned day 1 of treatment

- Patients must not have clinically significant cardiovascular or cerebrovascular
disease, including:

- Any history of

- Cerebrovascular disease including transient ischemic attack (TIA), stroke or
subarachnoid hemorrhage

- Ischemic bowel

- Within the last 12 months

- Myocardial infarction

- Unstable angina

- New York Heart Association (NYHA) class II or greater congestive heart
failure

- Grade II or greater peripheral vascular disease

- Uncontrolled hypertension defined as systolic blood pressure (SBP) > 160 or
diastolic blood pressure (DBP) > 90

- Uncontrolled or clinically significant arrhythmia

- NOTE: blood pressure must be obtained within =< 8 weeks prior to
randomization

- NOTE: patients with controlled atrial fibrillation are eligible

- Patients who require full-dose anticoagulation may enroll provided they meet the
following criteria:

- The patient must have an in-range international normalized ratio (INR) (usually
between 2 and 3) on a stable dose of warfarin or be on stable dose of low
molecular weight (LMW) heparin

- The patient must not have active bleeding or pathological conditions that carry
high risk of bleeding (e.g. varices)

- NOTE: prophylactic use of anticoagulants to maintain patency of a vascular
access device is permitted

- Patients must not have a bleeding diathesis, hereditary or acquired bleeding disorder
or coagulopathy

- Patients must not have a non-healing wound or fracture; patients with an abdominal
fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months
prior to randomization are not eligible

- Patients must not have hypersensitivity to paclitaxel or drugs using the vehicle
Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies

- Women must not be pregnant or breast-feeding; all females of childbearing potential
must have a blood or urine test within 7 days prior to randomization to rule out
pregnancy

- Women of childbearing potential and sexually active males must use an accepted and
effective method of contraception

Gender: Both
Steward Physician(s)
  • Kathy Miller
  • Ramona Swaby, MD
  • Donald W. Northfelt, MD, FACP
  • Chau T. Dang, MD
Facilities
  • St. Elizabeth's Medical Center - Active, not recruiting
Trial Interventions
Biological
  • Bevacizumab
Drug
  • Doxorubicin Hydrochloride
  • Cyclophosphamide
  • Paclitaxel
Other
  • Placebo
  • Laboratory Biomarker Analysis
  • Quality-of-Life Assessment
Physician Researcher

Investigator Name:

  • Kathy Miller
  • Ramona Swaby, MD
  • Donald W. Northfelt, MD, FACP
  • Chau T. Dang, MD

Other Information

Sponsor: National Cancer Institute (NCI)
Phase: Phase 3
Trial ID: NCT00433511
Volunteers:  Not Accepting Healthy Volunteers

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