Dose-Dense Chemotherapy Plus Bevacizumab in High Risk Lymph Node Positive Breast Cancer: A Pilot Study

Chap, Linnea I., M.D.

Status and phase

Unknown

Phase 2

Conditions

Breast Cancer

Treatments

Drug: bevacizumab combined with dose dense chemotherapy

Study type

Interventional

Funder types

Industry

Identifiers

NCT00378638

AVF3359s

Details and patient eligibility

About

This research focuses on women with breast cancer whose disease has not significantly progressed, but who have 5 or more lymph nodes involved. In this study subjects will receive bevacizumab, a drug which is FDA approved for colon cancer but not for breast cancer, in combination with a regimen of approved chemotherapy drugs known as "dose dense chemotherapy." The study will observe the effectiveness and tolerability of this regimen.

Full description

Approximately 200,000 women are diagnosed with breast cancer in the United States every year. A significant factor determining long-term survivability of breast cancer is whether or not lymph nodes, glands which cleanse and filter the body's fluids, are involved. Despite treatment with approved multiagent cytotoxic chemotherapy ("dose-dense chemotherapy"), women with breast cancer involving more than 4 axillary lymph nodes still have a high risk for recurrence.

Several dose-dense chemotherapy regimens are currently being compared in other studies, however, at this time there is no proof that one regimen is superior to another. Therefore, in an attempt to decrease metastases, prolong time to recurrence and improve overall survival, it is essential to develop novel therapeutic strategies. The use of inhibitors of angiogenesis represents a promising option.

Bevacizumab is the first angiogenesis inhibiting drug to be FDA approved, for the treatment of colon cancer. It is has also been studied alone in progressed lymph-node positive breast cancer and has shown moderate efficacy.

This study will observe the efficacy and tolerability of using bevacizumab in combination with an approved dose-dense chemotherapy regimen for 8 cycles, followed by 12 of bevacizumab alone. Patients may be on the study for up to 52 weeks if their disease has not progressed and the regimen is tolerated.

Enrollment

30 estimated patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

High risk lymph node positive breast cancer defined as 5 or more involved axillary lymph nodes
Must have undergone surgical local therapy (modified radical mastectomy or breast conserving surgery).
Negative tumor margins for invasive cancer
No evidence of distant metastasis
Normal cardiac ejection fraction
Adequate organ function defined as:

ANC > 1200/mm3 Platelet count > 100,000/mm Serum creatinine < 2.0 mg/dl Serum bilirubin < 1.5 x ULN

Performance status 0-1
Age 18 years or older
No prior chemotherapy, hormonal therapy or radiation therapy for treatment of the primary breast cancer
Bilateral synchronous breast cancer is allowed if other criteria are met.
Patients may be ER/PR+ and receive treatment with hormonal therapy (tamoxifen or aromatase inhibitors)
Use of effective means of contraception (men and women) in subjects of child-bearing potential
Signed informed consent

Exclusion criteria

Evidence of distant metastases
Inflammatory Breast Cancer
Prior use of any chemotherapy or hormonal therapy for breast cancer
Patients with her 2 neu positive tumors
History of other malignancies within the last 5 years. Prior history of carcinoma in situ of the cervix, melanoma in situ and basal cell carcinoma of the skin is allowed within the last 5 years.
Prior therapy with anthracyclines for any malignancy
Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
Blood pressure of equal to or higher than 150/100
Unstable angina
New York Heart Association (NYHA) Grade II or greater congestive heart failure
History of myocardial infarction within 6 months
History of stroke within 6 months
Clinically significant peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Presence of central nervous system or brain metastases
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
Pregnant (positive pregnancy test) or lactating
Urine protein:creatinine ratio >1.0 at screening
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
Serious, non-healing wound, ulcer, or bone fracture
Inability to comply with study and/or follow-up procedures