A Phase 1-2, XIAP Antisense AEG35156 With Weekly Paclitaxel in Patients With Advanced Breast Cancer

Inclusion Criteria:

• Patients with histologically or cytologically confirmed breast adenocarcinoma who are candidates for paclitaxel single agent chemotherapy for metastatic breast cancer
• ECOG performance < 2
• One or more metastatic tumors measurable by RECIST criteria on CT scan or MRI (Phase 2 part only)
• Life expectancy of at least 6 months
• Age > 18 years
• Signed, written IRB-approved informed consent
• A negative serum pregnancy test (if applicable)
• Acceptable liver function:
• Bilirubin within normal limit
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase < 2.0 times the institution's upper limit of normal
• Acceptable renal function:
• Serum creatinine within normal limits, OR calculated creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Acceptable hematologic status:
• Granulocyte > 1500 cells/uL
• Platelet count > 100,000 plt/uL
• Hemoglobin > 9.0 g/dL
• Acceptable coagulation status:
• PT within normal limits
• PTT within normal limits
• For women of child-bearing potential, the use of effective contraceptive methods during the study
• Prior radiotherapy is allowed provided disease progression outside the radiation field has been documented, and treatment completed at least 2 weeks prior to registration

Exclusion Criteria:

• Prior taxane chemotherapy for metastatic disease.
• More than one prior chemotherapy regimen for metastatic disease
• Active progressive brain metastases including the presence of any related symptoms or need for corticosteroids. A CT or MRI scan of the head is necessary in patients with a history of brain metastases to document the stability of prior lesions
• Grade > 2 peripheral neuropathy
• Known bleeding diathesis or concurrent treatment with anticoagulants except patients on non-therapeutic line maintenance coumadin
• Pregnant or nursing women. NOTE: Women of child-bearing potential must agree to use adequate contraception (sterile or surgically sterile; hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Known infection with HIV, hepatitis B, or hepatitis C
• Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
• Patients who are currently receiving any other investigational agent. Subjects who have used a previous antisense oligonucleotide in the last 90 days will be excluded
• Unwillingness or inability to comply with procedures required in this protocol
• Any deviation from these inclusion/exclusion criteria must be discussed with the sponsor prior to enrolling patient.