First Line Therapy for Patients With Metastatic Breast Cancer

An Open-Label, Phase II Study of Weekly ABI-007 as First Line Therapy for Patients With Metastatic Breast Cancer

The purpose of this study is to determine the toxicity and anti-tumor activity of nab-paclitaxel 100mg/m^2 administered weekly in a 4-week cycle as first line therapy to patients with metastatic breast cancer who received taxanes as part of their adjuvant therapy and patients who did not receive taxanes as part of their adjuvant therapy.

This is an open-label, phase II study to determine the toxicity and antitumor activity of ABI-007 100 mg/m2 administered weekly for 3 weeks followed by a rest week (4-week cycle) as first line therapy to patients with metastatic breast cancer in the following 2 cohorts: Patients who have received a taxane as part of their adjuvant therapy, and patients who did not receive a taxane as part of their adjuvant therapy. Patients will be assessed for antitumor response every 8 weeks.

The last subject received study treatment 11DEC2012. The study was terminated on 31 May 2013 via a notification letter to all investigators on 14 May 2013.

Inclusion Criteria:

• Females with pathologically confirmed adenocarcinoma of the breast.
• No prior chemotherapy for metastatic breast cancer
• At least 12 months between completion of adjuvant chemotherapy and the diagnosis of metastatic disease
• Stage IV disease
• Measurable disease (must be equal or greater to 2.0 cm using conventional Computed Tomography (CT) or equal or greater to 1.0 cm using spiral CT except for pulmonary lesions that are well documented on conventional CT scan which must be equal or greater than 1.0 cm)
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Age equal or greater to 18
• Patients has the following blood counts at Baseline:
• Absolute Neutrophil Count (ANC) equal or greater to 1.5 x 10^9 cells/L
• Platelets equal or greater to 100 x 10^9 cells/L
• Hemoglobin (Hgb) equal or greater to 90 grams/L
• Patients has the following blood chemistry levels at Baseline:
• Aspartate aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT) serum glutamic:pyruvic transaminase (SGPT)less than or equal to 2.5x upper limit of normal range (ULN);
• total bilirubin normal (unless bilirubin elevation is due to Gilbert's (Disease);
• alkaline phosphatase less than or equal 2.5x ULN (unless bone metastasis is present in the absence of liver metastasis);
• Creatinine less than or equal to 1.5mg/dL
• Current sensory neuropathy Grade 0 or 1 by Breast Cancer Index (BCI) Common Toxicity Criteria Adverse Events (CTCAE)
• 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 of contraception to avoid pregnancy for the duration of the study
• Patient is able to supply unstained slides or 1 tumor block of her primary breast tumor or a biopsy of a current site of metastasis for Secreted protein acidic and rich in cysteine (SPARC) analysis
• Informed consent has been obtained

Exclusion Criteria:

• Concurrent immunotherapy or hormonal therapy (other than Herceptin) 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 diagnoses or assessment of breast cancer, with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• 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 Taxol or Taxotere