A Phase I/II Study of ABI-007 (Abraxane®, Nab®-Paclitaxel)and Vinorelbine in Patients With Stage IV (Metastatic) Breast Cancer
A Phase I/II Study of ABI-007 (Abraxane®, Nab®-Paclitaxel)and Vinorelbine in Patients With Stage IV (Metastatic) Breast Cancer
The purpose of this study is to: 1) determine the optimal tolerated dose of ABI-007 and
 vinorelbine, given concurrently on a weekly basis, in the absence of planned growth factor
 support with granulocyte colony-stimulating factor (G-CSF) (Patients with HER-2/neu positive
 disease may receive Herceptin, and 2) determine the optimal tolerated dose of ABI-007 and
 vinorelbine, given concurrently on a weekly basis, in the presence of planned growth factor
 support with G-CSF.
Inclusion Criteria:

 -  Patient has microscopically confirmed invasive breast carcinoma with clinical and/or
 radiographic evidence of stage 4 disease. If diagnosis is based on pleural effusion,
 positive cytology must be confirmed.

 -  Patient has had no prior chemotherapy for Stage 4 disease (hormone therapy is
 permitted). Prior adjuvant paclitaxel by 3-hour infusion is permitted, if there is no
 residual neuropathy. Prior adjuvant docetaxel on an every 3 week schedule is
 permitted.

 -  Disease must be measurable (unidimensional by Response Evaluation Criteria In Solid
 Tumors (RECIST) criteria) or evaluable (e.g., malignant effusion, marrow involvement).
 Elevated tumor markers alone are insufficient.

 -  Age >18.

 -  Southwest Oncology Group (SWOG)/Eastern Oncology Group (ECOG) performance status must
 be < or =2 at screen and on treatment day one.

 -  Life expectancy must be estimated at >16 weeks.

 -  Prior irradiation is permitted, provided:

 -  Does not exceed 25% of the estimated bone marrow volume

 -  Measurable/evaluable disease exists outside the radiation field, or progressive
 disease is documented within the radiation field.

 -  Informed consent must be obtained prior to registration.

 -  Patients must be > 2 weeks from prior surgery; > 3 weeks from radiation therapy to the
 pelvis, spine or long bones; > 3 weeks from prior chemotherapy (> 6 weeks for
 mitomycin C or nitrosureas), or > 2 weeks from prior hormonal therapy.

 -  All patients must have placement of appropriate central venous access device.

 -  Tumor HER2/neu expression must be determined prior to study enrollment. Assessment may
 be by fluorescence in situ hybridization (FISH) assay or by immunohistochemistry
 (ICC). If determination is intermediate by ICC, FISH must be performed. For enrollment
 purposes, this phase I study will not discriminate based on HER2 status. However,
 documentation of patients' HER2 status will be maintained and Herceptin will be
 prescribed for all HER2 positive patients.

 Exclusion Criteria:

 -  Granulocytes < 1,500/mm^3.

 -  Platelets < 100,000/mm^3.

 -  Hemoglobin < 9 gm/dl.

 -  Creatinine > 2.0 mg/dl.

 -  Total bilirubin > 2 mg/dl.

 -  Visceral crisis characterized by rapidly progressive hepatic or lymphangitic lung
 metastases.

 -  Medically unstable as judged by the patient's physician.

 -  Pregnancy or lactation; failure to employ adequate contraception.

 -  Uncontrolled central nervous system (CNS) disease.

 -  Pre-existing Grade ≥ 2 peripheral neuropathy except for abnormalities due to cancer.

 -  Psychological, familial, sociological or geographical conditions which do not permit
 weekly medical follow-up and compliance with the study protocol.

 -  Prior therapy with vinorelbine or prior therapy with a taxane that resulted in
 neuropathy.