Bevacizumab to Treat Inflammatory Breast Cancer or Locally Advanced Breast Cancer

NCT00016549 | Completed Phase 2

• 2 other identifiers: 01017301-C-0173
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effectiveness of the drug bevacizumab, in combination with doxorubicin and docetaxel, in improving survival of patients with inflammatory breast cancer or locally advanced breast cancer. Inflammatory breast cancer is an aggressive form of locally advanced breast cancer that often causes a red, swollen, tender breast and is associated with a poor prognosis. Bevacizumab blocks the growth of new blood vessels that supply oxygen and nutrients to tumors, and therefore, may kill cancer cells or stop their growth. Doxorubicin and docetaxel are approved drugs for treating breast cancer. Patients 18 years of age or older with stage inflammatory breast cancer who have not been treated with chemotherapy or radiation therapy may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, chest x-ray, electrocardiogram, and MUGA scan or echocardiography (see below). A mammogram of both breasts, dynamic MRI imaging of the affected breast, computed tomography (CT) of the head, chest, abdomen and pelvis, and a bone scan are done to determine the extent of disease. Participants undergo the following procedures at various intervals before, during and/or after completing chemotherapy: Tumor and skin biopsies to study the effects of bevacizumab on tumor blood vessels, tumor growth, and the biology of inflammatory breast cancer. A small piece of tumor tissue and a small piece of skin from the affected breast are removed under local anesthesia for microscopic study. Dynamic MRI to examine changes in the blood vessels and breast cancer following bevacizumab treatment. This test involves injecting a contrast liquid into a vein before scanning. A standard MRI scan is done before the dynamic MRI. Blood tests are done to 1) study clot formation and breakdown, 2) measure levels of VEGF (a substance produced by breast cancer cells) and VCAM-1 (a substance produced by cells lining blood vessel walls), and 3) check blood counts and liver and kidney function. MUGA (a nuclear medicine scan that checks the heart's pumping ability) or echocardiogram (ultrasound scan of the heart to evaluate heart function. Blood pressure monitoring Urine tests CT scans and x-rays to evaluate disease before and after treatment. Patients will have a central venous line (plastic tube) placed into a major vein in the chest before beginning treatment. The line stays in the body during the entire treatment period and is used to give chemotherapy and other medications, if needed, and to draw blood samples. All treatment is given on a single day every 3 weeks. This constitutes one treatment cycle. Cycle 1 consists of bevacizumab alone; cycles 2 through 7 consist of bevacizumab with doxorubicin and docetaxel. During each cycle, patients also receive injections under the skin of G-CSF, a drug that raises the number of infection-fighting white blood cells, which are often decreased as a side effect of chemotherapy. After cycle 7, patients may require surgery and radiation or radiation alone. After radiation treatment, bevacizumab is re-started, given alone every 3 weeks for an additional eight cycles. Patients whose tumors are positive for estrogen or progesterone receptors will be advised to take the drug tamoxifen or anastrozole for 5 years to decrease the chances of disease recurrence. This would begin with cycle 8.

Conditions

Breast Cancer

Keywords

Endothelial Proliferation; Endothelial Apoptosis; VEGF; Magnetic Resonance Imaging; Molecular Targets; Breast Cancer; Inflammatory Breast Cancer; IBC

Outcome Measures

Primary Outcomes (1)

• To determine in IBC or LABC whether a change in any of the 4 angiogenesis parameters; 3 primary molecular parameters or the dynamic MRI parameter can be detected from baseline to 3 wks after treatment with bevacizumab.

Secondary Outcomes (1)

• To attempt to correlate each of the four primary parameters with clinical findings and time to progression/recurrence.

Interventions

Bevacizumab BIOLOGICAL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have inflammatory breast cancer or locally advanced breast cancer previously untreated with chemotherapy and/or radiation therapy. Inflammatory breast cancer is defined as histologically proven invasive adenocarcinoma of one breast with clinical inflammatory signs including onset of erythema and brawny induration or edema of the skin with an erysipeloid edge with or without an underlying tumor mass. Dermal lymphatic involvement by tumor cells is not a requirement for diagnosis. We will define locally advanced breast cancer as stage IIB, IIIA, or IIIC breast cancer according to the 2002 AJCC staging guidelines. Patients must have tissue accessible for serial biopsies.
• Age greater than or equal to 18 years.
• ECOG performance status of 0, 1, or 2.
• Patients must have a left ventricular ejection fraction of greater than or equal to 50% without clinical symptoms or signs of heart failure.
• Patients must have adequate bone marrow, hepatic and renal function as defined by the following:
• Absolute neutrophil count greater than or equal to 1500/mL; Platelets greater than or equal to 100,000/mL; Serum creatinine less than or equal to 1.5 mg/dL; AST, ALT less than or equal to 1.5 times the upper limit of normal; Alkaline phosphatase less than or equal to 2.5 times the upper limit of normal; Total bilirubin less than or equal to the upper limit of normal for institution. In patients with evidence of Gilbert's disease, elevated bilirubin should not be related to tumor or other liver diseases, and should be less than or equal to 2 times the upper limit of normal.
• Women of childbearing potential must agree to use an accepted and effective method of contraception during their participation on the trial.
• Patients must be able to provide informed consent.

You may not qualify if:

• Evidence of carcinomatous meningitis or brain metastases or other CNS disease including history of stroke, primary brain tumor or seizures not controlled by standard medical therapy.
• History of an active malignancy other than in situ carcinoma of the cervix, or non-melanomatous skin cancers in the last five years prior to Day 1 on study.
• Patients with non-healing wounds, bone fractures, or major surgery within the previous 28 days..
• Uncontrolled hypertension (sustained systolic blood pressure greater than 160 mmHg or diastolic blood pressure of greater than 100 mmHg).
• Clinically significant cardiovascular disease (e.g., myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or Grade II or greater peripheral vascular disease within 12 months prior to Day 1 on study.
• INR greater than 1.50. Prior history of bleeding diathesis or coagulopathy including deep venous thrombosis or pulmonary embolism. Recent (within last six months) or current history of gastrointestinal bleeding.
• Current use of full-dose or parenteral anticoagulants or chronic daily treatment with aspirin (greater than 325 mg/day) within 10 days prior to Day 1 on study.
• Active infection requiring intravenous antibiotics on Day 1 on study.
• Patients with 24 hour urine protein greater than or equal to 500 mg or a history of a primary renal disease (excluding infection).
• Clinical grade greater than or equal to 2 peripheral neuropathy.
• History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
• Pregnant or lactating women.
• Patients who are receiving other investigational drugs.
• Patients with a history of hypersensitivity reaction to products containing Polysorbate 80 (Tween 80).
• Patients with a known hypersensitivity to E. coli derived products.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4-25. doi: 10.1210/edrv.18.1.0287. No abstract available.

  PMID: 9034784 BACKGROUND

• Paweletz N, Knierim M. Tumor-related angiogenesis. Crit Rev Oncol Hematol. 1989;9(3):197-242. doi: 10.1016/s1040-8428(89)80002-2.

  PMID: 2480145 BACKGROUND

• Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4-6. doi: 10.1093/jnci/82.1.4. No abstract available.

  PMID: 1688381 BACKGROUND

• Thukral A, Thomasson DM, Chow CK, Eulate R, Wedam SB, Gupta SN, Wise BJ, Steinberg SM, Liewehr DJ, Choyke PL, Swain SM. Inflammatory breast cancer: dynamic contrast-enhanced MR in patients receiving bevacizumab--initial experience. Radiology. 2007 Sep;244(3):727-35. doi: 10.1148/radiol.2443060926.

  PMID: 17709827 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Suparna Wedam, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 16, 2001
• First Posted: May 17, 2001
• Study Start: May 13, 2001
• Primary Completion: January 29, 2007
• Study Completion: January 29, 2007
• Last Updated: July 2, 2017

Record last verified: 2012-04-06

Locations

US (1)