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Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI, Other	CDR0000434634 ECOG-E2104, NCT00119262

Trial Description

Summary

RATIONALE: 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 tumor cells by blocking blood flow to the tumor. 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 bevacizumab together with more than one chemotherapy drug (combination chemotherapy), may be a better way to block tumor growth.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with combination chemotherapy works in treating patients who have undergone surgery for breast cancer that has spread to the lymph nodes.

Further Study Information

OBJECTIVES:

Primary

• 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.

Secondary

• Determine the changes in left ventricular ejection fraction in patients treated with this regimen.

• 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 groups.

• Group I: 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 (SC) 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.

• Group II: 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 toxicity.

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 ER- and/or 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.

NOTE: *Premenopausal patients may participate in SOFT, TEXT, or PERCHE clinical trials.

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

PROJECTED ACCRUAL: A total of 212 patients (106 for group I and 106 for group II) will be accrued for this study within 1.4-6.7 months.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• 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

• Patients with immunohistologic staining as the only evidence of nodal involvement are not eligible

• 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 (group I only)

• Surgical margins must be histologically free of invasive tumor AND ductal carcinoma in situ

• Lobular carcinoma in situ allowed

• Synchronous bilateral breast cancer diagnosed within the past month allowed provided the higher TNM stage tumor meets study eligibility criteria

• No HER2/neu-positive disease (i.e., 3+ by immunohistochemistry or positive by fluorescent in situ hybridization)

• No clinical evidence of inflammatory disease or fixed axillary nodes (N2)

• Hormone receptor status:

• Any receptor status allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

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

• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL

• AST ≤ 2 times upper limit normal (ULN)

• PT INR ≤ 1.5 times normal

• PTT ≤ 1.5 times normal

Renal

• Creatinine ≤ 1.5 mg/dL

• Urine protein:creatinine ratio < 1.0

Cardiovascular

• LVEF normal by MUGA or echocardiogram

• No history of myocardial infarction within the past year

• No history of unstable angina within the past year

• No history of arterial thrombotic events within the past year

• No uncontrolled or clinically significant arrhythmia

• No New York Heart Association grade II-IV congestive heart failure

• No peripheral vascular disease ≥ grade II

• No uncontrolled hypertension, defined as systolic blood pressure (BP) > 160 mm Hg or diastolic BP > 90 mm Hg

• No history of deep venous thrombosis

• No history of cerebrovascular disease, including transient ischemic attack or stroke

• No other clinically significant cardiovascular disease

Pulmonary

• No history of pulmonary embolism

Other

• Not pregnant

• No nursing during and for ≥ 3-4 months after completion of study treatment

• Negative pregnancy test

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

• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

• No non-healing wound or bone fracture

• No hypersensitivity to paclitaxel or drugs using Cremophor

• No hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior cytotoxic chemotherapy for breast cancer

• No prior anthracycline, anthracenedione, or taxane for any condition

Endocrine therapy

• No prior hormonal therapy for breast cancer

• Prior tamoxifen or raloxifene for chemoprevention allowed

• No other concurrent tamoxifen or raloxifene

Radiotherapy

• No prior radiotherapy for breast cancer

• No concurrent radiotherapy to the internal mammary chain

Surgery

• See Disease Characteristics

• More than 4 weeks since prior major surgery

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

Other

• No concurrent therapeutic anticoagulants

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

• No 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*

• No other concurrent drugs known to inhibit platelet function, including any of the following:

• Dipyridamole

• Ticlopidine

• Clopidogrel

• Cilostazol

• No concurrent cardioprotectant agents NOTE: *Regular use of cyclo-oxygenase-2 inhibitors or low-dose aspirin allowed

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

Kathy Miller

Study Chair

Robin Zon

Edith A. Perez

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00119262
Information obtained from ClinicalTrials.gov on October 06, 2009

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