Phase II Trial Comparing ABI-007 (Abraxane®, Nab®-Paclitaxel) to Taxotere in First Line Therapy of Patients With Stage IV Breast Cancer

A Randomized Phase II Study of Weekly or Every 3 Weeks ABI-007 Versus Every 3 Weeks Taxotere as First Line Therapy of Stage IV (Metastatic) Breast Cancer

This was an open-label study conducted comparing the toxicity and antitumor activity of ABI-007 (Abraxane®, nab®-paclitaxel) to docetaxel (Taxotere).

This was an open-label, randomized study to compare the following regimens with respect to toxicity and antitumor activity:

• the maximum tolerated dose (MTD) of ABI-007 300 mg/m^2 every 3 weeks;
• ABI-007 100 mg/m^2 administered weekly for 3 weeks with a 1 week rest;
• ABI-007 150 mg/m^2 administered weekly for 3 weeks with a 1 week rest;
• the standard dose and schedule of Taxotere (100 mg/m^2 every 3 weeks).

Inclusion Criteria:

Patients had to meet the following criteria to be eligible for the study:

1. Pathologically confirmed adenocarcinoma of the breast.

2. No prior chemotherapy for metastatic breast cancer.

3. Stage IV disease.

4. Measurable disease (must have been ≥ 2.0 cm, except for pulmonary lesions that were well documented on CT scan that were ≥ 1.0 cm).

5. At least 3 weeks since prior cytotoxic chemotherapy (patients should have recovered from all acute effects of such therapy.

6. At least 4 weeks since radiotherapy, with full recovery. The measurable disease was completely outside the radiation portal or there was radiologic or clinical exam proof of progressive disease within the radiation portal.

7. At least 4 weeks since major surgery, with full recovery.

8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

9. Age ≥18 years.

10. Patient had the following blood counts at Baseline:

    • Absolute neutrophil count (ANC) ≥1.5*10^9 cells/L
    • Platelets ≥100*10^9 cells/L
    • Hemoglobin (Hgb) ≥9 g/dL.

11. Patient had the following baseline blood chemistry levels:

    • Aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT])≥2.5x upper limit of normal (ULN) range
    • Total bilirubin normal
    • Alkaline phosphatase ≥2.5x ULN (unless bone metastasis is present in the absence of liver metastasis)
    • Creatinine ≥1.5 mg/dL.

12. Peripheral neuropathy Grade 0 or 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

13. If female of childbearing potential, pregnancy test was negative (within 72 hours of the first dose of study drug).

14. If fertile, the patient agreed to use an effective method to avoid pregnancy for the duration of the study.

15. Informed consent had been obtained.

Exclusion Criteria:

Patients who met any of the following criteria were excluded from the study:

1. Prior neo-adjuvant or adjuvant chemotherapy was allowed. No prior chemotherapy for metastatic disease was allowed. If a taxane was part of the adjuvant regimen, at least one year should have transpired since completion of taxane regimen.
2. Cumulative life-time dose of doxorubicin >360 mg/m^2. Doxorubicin was allowed as prior neo-adjuvant or adjuvant therapy but not for metastatic disease.
3. Concurrent immunotherapy or hormonal therapy for breast cancer.
4. Parenchymal brain metastases, unless documented to be clinically and radiographically stable for at least 6 months after treatment.
5. Serious intercurrent medical or psychiatric illness, including serious active infection.
6. History of class II-IV congestive heart failure.
7. History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
8. Patients who had received an investigational drug within the previous 3 weeks.
9. Patient was enrolled in a different clinical study in which investigational procedures were performed or investigational therapies were administered. Also, a patient was not permitted enroll in such clinical trials while participating in this study.
10. Pregnant or nursing women
11. Patients with prior hypersensitivity to either Taxol or Taxotere.