A Phase I/II Study of GRN163L in Combination With Paclitaxel and Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the breast with
measurable locally recurrent or metastatic disease

- May have had one prior non-taxane chemotherapy regimen for metastatic disease

- If HER2 positive, must have had prior treatment with trastuzumab (Herceptin®)

- If previously treated with an anthracycline, anthracenedione, or trastuzumab must be
tested by MUGA scan or echocardiogram and have LVEF ≥ 50%

- Must have recovered from most recent radiation treatment or surgical procedure

- ECOG performance status of 0 or 1

- Life expectancy ≥ 3 months

Exclusion Criteria:

- Locally recurrent disease amenable to resection with curative intent

- Prior adjuvant or neoadjuvant taxane chemotherapy within 12 months prior to first
study drug administration

- Investigational therapy within 4 weeks prior to first study drug administration

- Prior hormonal therapy within 2 weeks prior to first study drug administration

- Prior radiotherapy within 2 weeks prior to first study drug administration

- Cytotoxic chemotherapy within 2 weeks prior to first study drug administration

- Therapeutic anticoagulation or regular use of anti-platelet therapy within 2 weeks
prior to first study drug administration NOTE: Low-dose anticoagulant therapy to
maintain patency of a vascular access device is allowed.

- Prolongation of PT or INR, aPTT > ULN, or fibrinogen < LLN

- Active or chronically current bleeding (eg, active peptic ulcer)

- Clinically significant cardiovascular or cerebrovascular disease including

Any history of:

- Cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage

- Ischemic bowel

Within the last 12 months:

- MI

- Unstable angina

- NYHA grade II or greater CHF

- Grade 2 or greater peripheral vascular disease

Active at study entry:

- Uncontrolled hypertension defined as SBP > 160 or DBP > 90

- Uncontrolled or clinically significant arrhythmia

- Clinically relevant active infection

- Nonhealing wound or fracture

- Serious co-morbid medical conditions, including cirrhosis and chronic obstructive or
chronic restrictive pulmonary disease

- Active autoimmune disease requiring immunosuppressive therapy

- Known positive serology for HIV

- Prior malignancy (within the last 3 years) except for adequately treated basal cell
or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, or in
situ prostate cancer, or other cancer for which the patient has been disease-free for
at least 3 years

- Any other severe, acute, or chronic medical or psychiatric condition, laboratory
abnormality, or difficult complying with protocol requirements that may increase the
risk associated with study participation or study drug administration or may
interfere with the interpretation of study results and, in the judgment of the
investigator, would make the patient inappropriate for this study