Phase II Trial Comparing ABI-007 to Taxotere in First Line Therapy of Patients With Stage IV Breast Cancer

This is an open-label study conducted at study sites in Russia and the Ukraine comparing the toxicity and antitumor activity of ABI-007 to Taxotere.

This is an open-label, randomized study to compare the following regimens with respect to toxicity and antitumor activity: the MTD of ABI 007 for a q3w schedule (300 mg/m2 every 3 weeks); ABI-007 100 mg/m2 administered weekly for 3 weeks with a 1 week rest; ABI-007 150 mg/m2 administered weekly for 3 weeks with a 1 week rest; and the standard dose and schedule of Taxotere (100 mg/m2 every 3 weeks).

• Experimental: ABI-007 100
  Weekly or every 3 weeks ABI-007 versus every 3 weeks Taxotere
  Intervention: Drug: Araxane versus Taxotere
• Experimental: ABI-007 150
  Arm 2
  Intervention: Drug: Araxane versus Taxotere
• Experimental: ABI-007 300
  Arm 3
  Intervention: Drug: Araxane versus Taxotere

Inclusion Criteria:

• Pathologically confirmed adenocarcinoma of the breast.
• No prior chemotherapy for metastatic breast cancer.
• Stage IV disease
• Measurable disease
• At least 3 weeks since prior cytotoxic chemotherapy(patients should have recovered from all acute effects of such therapy.
• At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be radiologic or clinical exam proof of progressive disease within the radiation portal.
• At least 4 weeks since major surgery, with full recovery.
• ECOG performance status 0-2.
• Age ≥18 years.
• 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.
• Patient has the following blood chemistry levels at Baseline:
• AST (SGOT), ALT (SGPT)≥2.5x upper limit of normal range (ULN);
• Total bilirubin normal;
• Alkaline phosphatase ≥2.5x ULN (unless bone metastasis is present in the absence of liver metastasis);
• Creatinine ≥1.5 mg/dL.
• Peripheral neuropathy Grade 0 or 1.
• If female of childbearing potential, pregnancy test is negative (within 72 hours of the first dose of study drug).
• If fertile, the patient agrees to use an effective method to avoid pregnancy for the duration of the study.
• Informed consent has been obtained

Exclusion Criteria:

• Prior neo-adjuvant or adjuvant chemotherapy is allowed. No prior chemotherapy for metastatic disease is allowed. If a taxane was part of the adjuvant regimen, at least one year should have transpired since completion of taxane regimen.
• Cumulative life-time dose of doxorubicin >360 mg/m2. Doxorubicin is allowed as prior neo-adjuvant or adjuvant therapy but not for metastatic disease.
• Concurrent immunotherapy or hormonal therapy for breast cancer.
• Parenchymal brain metastases, unless documented to be clinically and radiographically stable for at least 6 months after treatment.
• Serious intercurrent medical or psychiatric illness, including serious active infection.
• History of class II-IV congestive heart failure.
• History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
• Patients who have received an investigational drug within the previous 3 weeks.
• Patient is currently enrolled in a different clinical study in which investigational procedures are performed or investigational therapies are administered. Also, a patient may not enroll in such clinical trials while participating in this study.
• Pregnant or nursing women
• Patients with prior hypersensitivity to both Taxol and Taxotere.