Fresolimumab and Radiotherapy in Metastatic Breast Cancer

Inclusion Criteria

• Biopsy-proven breast cancer, metastatic (persistent or recurrent).
• Failed ≥1 line of therapy (endocrine or chemotherapy) for metastatic disease.
• Min. 3 distinct metastatic sites, at least one measurable lesion which is at least 1 cm or larger in largest diameter.
• Must be ≥4 weeks since all of the following treatments (recovered from toxicity of prior treatment to ≤Grade 1, excluding alopecia):
• major surgery;
• radiotherapy;
• chemotherapy (≥6 weeks since therapy if a nitrosourea, mitomycin, or monoclonal antibodies such as bevacizumab);
• immunotherapy;
• biotherapy/targeted therapies.
• >18 years of age.
• Life expectancy >6 months.
• Eastern Cooperative Oncology Group (ECOG) status 0 or 1.
• Adequate organ function including:
• Hemoglobin ≥10.0g/dL, absolute neutrophil count (ANC) ≥1,500/mm3, and platelets ≥100,000/mm3.
• Hepatic: Serum total bilirubin ≤1.5x upper limit of normal (ULN) (Patients with Gilbert's Disease may be included if total bilirubin is ≤3.0mg/dL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2.5xULN. If patient has known liver metastases, ALT and/or AST ≤5xULN are allowed.
• Renal: creatinine clearance ≥60mL/min.
• Prothrombin (PT) and partial thromboplastin times (PTT) 38.5°C).
• Systemic autoimmune disease (e.g. systemic lupus erythematosus, active rheumatoid arthritis).
• Known allergy to any component of GC1008.
• Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding, or anti-coagulation therapy (including anti platelet agents i.e. aspirin, clopidogrel, ticlopidine, dipyridamole, other agents inducing long-acting platelet dysfunction). Patients with history of deep venous thrombosis are allowed if treated, completely resolved, and no treatment for >4months.
• Calcium >11.0mg/dL (2.75mmol/L) unresponsive or uncontrolled in response to standard therapy (e.g. bisphosphonates).
• Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems, including, but not limited to:
• Other serious non-malignancy-associated conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs;
• Conditions, psychiatric, substance abuse, or other, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study;
• Pregnant or nursing women.