Trial Information

Summary: A study to compare 3 different treatment schedules of ABI-007 (Abraxane™) in combination with bevacizumab in women with metastatic breast cancer

This is a multi-center, randomized, open label phase II trial evaluating the antitumor activity and safety of the following regimens in patients who have not previously had chemotherapy for their metastatic breast cancer:

A total of 225 patients will be randomized into one of 3 treatment groups:

Arm A will receive 260 mg/m² of ABI-007 and 15 mg/kg bevacizumab every 3 weeks
Arm B will receive 260 mg/m² of ABI-007 and 10 mg/kg bevacizumab every 2 weeks with prophylactic GCSF support.
Arm C will receive 130 mg/m² of ABI-007 weekly with no interruption, with 10 mg/kg bevacizumab every 2 weeks.

Therapy will continue in the absence of disease progression and unacceptable toxicity

A patient will be eligible for inclusion in the study if all of the following are met:

1. Pathologically confirmed adenocarcinoma of the breast.
2. Stage IV disease (see Appendix III).
3. Measurable disease (defined as the presence of at least one lesion that can be accurately measured in at least one dimension with longest diameter = 2.0 cm using conventional techniques or = 1.0 cm with spiral CT scan).
4. Patients must not be a candidate for Herceptin therapy (i.e., patients with HER-2 positive disease (gene amplification by FISH or 3+ overexpression by IHC) and patients with unknown HER-2 status are ineligible unless the treating physician has determined that Herceptin-based therapy would be inappropriate or not indicated).
5. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease within the radiation portal.
6. At least 4 weeks since major surgery, with full recovery.
7. ECOG performance status 0-2.
8. Female >18 years of age.
9. Patient has the following blood counts at Baseline:

• ANC = 1.5 x 10⁹ cells/L;
• platelets = 100 x 10⁹ cells/L;
• Hgb = 9 g/dL.

10. Patient has the following blood chemistry levels at Baseline:

• AST (SGOT), ALT (SGPT) = 2.5x upper limit of normal range (ULN);
• total bilirubin = ULN;
• creatinine = 1.5 mg/dL.

11. If female of childbearing potential, pregnancy test is negative within 72 hours of first dose of study drug.
12. If fertile, the patient agrees to use an effective method to avoid pregnancy for the duration of the study.
13. Informed consent has been obtained.

A patient will not be eligible for the study if any of the following apply:

1. Prior neo-adjuvant or adjuvant chemotherapy is allowed, and patients must have recovered from the acute toxicity of such therapies. No prior chemotherapy for metastatic disease is allowed. If a taxane was part of the adjuvant regimen, at least 12 months should have passed from completion of taxane regimen to relapse. If a non-taxane-based adjuvant chemotherapy was administered, at least 6 months should have passed from completion to relapse.
2. Concurrent immunotherapy or hormonal therapy.
3. Parenchymal brain metastases, including leptomeningeal involvement.
4. Inadequately controlled hypertension (defined as blood pressure of > 150/100 mmHg) or NYHA Grade 2 or greater congestive heart failure.
5. Any prior history of hypertensive crisis or hypertensive encephalopathy.
6. History of myocardial infarction or unstable angina within 6 months prior to study enrollment.
7. History of stroke or transient ischemic attack within 6 months prior to study enrollment.
8. Significant vascular disease (e.g., aortic aneurysm, aortic dissection).
9. Symptomatic peripheral vascular disease.
10. Evidence of bleeding diathesis or coagulopathy.
11. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
12. Proteinuria at screening as demonstrated by either:

• Urine protein:creatinine (UPC) ratio > 1.0 at screening OR
• Urine dipstick for proteinuria = 2+ (patients discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate = 1g of protein in 24 hours to be eligible).

13. Known hypersensitivity to any component of bevacizumab.
14. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to first dose.
15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose, anticipation of need for major surgical procedure during the course of the study. Serious, non-healing wound, ulcer, or bone fracture. Serious intercurrent medical or psychiatric illness, including serious active infection.
16. History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
17. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
18. Pregnant or nursing women.
19. Sensory neuropathy of > Grade 1 at baseline.

If you would like to learn more about participating in this study, please send an e-mail message using the form below.