fresolimumab and radiotherapy in metastatic breast cancer

Conditions: Metastatic Breast Cancer

Summary: the purpose of this study is to test safety of combining fresolimumab and local radiotherapy and to see if the combination can achieve tumor regression.


Eligibility criteria:
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) \<uln. * negative for hepatitis viruses b and c unless consistent with prior vaccination or prior infection with full recovery. * patients of childbearing potential must agree to use effective contraception while on study, and for ≥3 months after last treatment. * understand and sign written informed consent document. no consent by durable power of attorney. exclusion criteria: * second malignancy - unless following curative intent therapy, has been disease free for ≥2 years with probability of recurrence \<5%. curatively treated early-stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (cin) are allowed. * concurrent cancer therapy. * uncontrolled central nervous system (cns) metastases, meningeal carcinomatosis, malignant seizures, or disease that causes or threatens neurologic compromise (e.g. unstable vertebral metastases). * history of ascites or pleural effusions, unless successfully treated. * organ transplant, including allogeneic bone marrow transplant. * immunosuppressive therapy including: * systemic corticosteroid therapy, including replacement therapy for hypoadrenalism. inhaled or topical corticosteroids are allowed (if therapy is \<5 days and is limited to systemic steroids as antiemetics); * cyclosporine a, tacrolimus, or sirolimus. * investigational agents within 4 weeks prior to study enrollment (≥6 weeks if treatment was long-acting agent such as monoclonal antibody). * significant or uncontrolled medical illness, e.g. congestive heart failure (chf), myocardial infarction, symptomatic coronary artery disease, significant ventricular arrhythmias within the last 6 months, or significant pulmonary dysfunction. patients with remote history of asthma or active mild asthma may participate. * active infection, including unexplained fever (\>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.

Keywords: metastatic breast cancer tgf-beta fresolimumab monoclonal antibody radiation therapy abscopal response