Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Women w/ histologically/cytologically confirmed breast carcinoma
Documented progressive metastatic disease not amenable to curative surgery/radiotherapy
Age ≥18 and ≤70 years

Prior treatments that included capecitabine and both an anthracycline and a taxane drug and resistant to taxane therapy

ER+ patients: minimum cumulative dose of anthracycline (≥ 180 mg/m² of doxorubicin or ≥ 300 mg/m² of epirubicin) or resistance to anthracycline, capecitabine and anti-hormonal therapy
Resistance is defined as tumor progression while receiving treatment or progression within 4 months of the last dose in the metastatic setting, or recurrence within 12 months in the neoadjuvant/adjuvant setting
Post-menopausal ER+ and/or PR+ must have received at least 2 lines of prior anti-estrogen therapy, which includes an aromatase inhibitor
Her2+ patients: at least 1 Her2+ targeted regimen containing trastuzumab alone or with pertuzumab/lapatinib. Trastuzumab/pertuzumab must have been discontinued at least 4 weeks before treatment
Prior radiation therapy completed >4 weeks before treatment
Measurable disease according to revised RECIST v.1.1 guidelines with at least 1 lesion deemed to be safely accessible for serial biopsy
ECOG <2

Adequate hematological function

Absolute granulocyte count ≥ 1,500/mm3
Platelet count ≥ 100,000/mm3
PT/INR ≤ 1.5
INR correctable to ≤ 1.5 or a PT/PTT correctable to normal limits. Patients receiving anti-coagulation treatment with agent such as warfarin/heparin may participate. For patients on warfarin, INR should be monitored weekly prior to any intervention to assure INR is stable. Heparin/warfarin must be withheld before biopsy
Hemoglobin ≥ 9 g/dL (may be corrected by transfusion)

Adequate organ function

Creatinine ≤ 1.5 mg/dL
Total bilirubin ≤ 1.5 times ULN
Alkaline phosphatase≤2.5 times ULN (≤5 times normal if liver involvement)
Aspartate aminotransferase (AST/SGOT) ≤ 5.0 times ULN
Alanine aminotransferase (ALT/SGPT) ≤ 5.0 times ULN
EKG without clinically relevant abnormalities
Pre-menopausal with child bearing potential subjects must use adequate contraception
Informed consent in the native language of the subject

Exclusion Criteria:

Peritoneal carcinomatosis
Moderate-large ascites accumulation requiring/likely to require paracentesis
Clinical/radiological evidence of brain metastasis/leptomeningeal involvement
Pulmonary lymphangitis/symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment
History of 2nd primary malignancy, except: bilateral breast carcinoma, in situ carcinoma of the cervix, adequately treated non-melanomatous carcinoma of the skin, and other malignancy treated at least 5 years with no evidence of recurrence
>3 prior chemotherapy regimens for metastatic disease
History of severe hypersensitivity to monoclonal antibody drugs/any contraindication to study drugs
Pregnant or breast feeding
Any serious, concurrent uncontrolled medical disorder
Prior hepatectomy, liver chemoembolization, liver cryoablation/ radiofrequency ablated
Symptomatic pulmonary disease
Bevacizumab (Avastin®) within 3 weeks of accrual
Prior allogeneic bone marrow/stem cell or solid organ transplant
Chronic use (> 2 weeks) of greater than physiologic doses of corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 30 days of the first day of study treatment. Topical and inhaled corticosteroids are permitted
Concomitant active autoimmune disease
Prior experimental therapy/cancer vaccine treatment
Current immunosuppressive therapy, including: cyclosporine, antithymocyte globulin, or tacrolimus within 1 month of study entry
History of blood transfusion reactions
Known allergy to bovine products
Know allergy to murine products
Progressive viral/bacterial infection. All infections must be resolved and the patient must remain afebrile for 7days without antibiotics prior to enrollment
Cardiac disease of symptomatic nature or cardiac ejection fraction < 45%
History of HIV positivity or AIDS
Psychiatric/addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation
Concurrent medication known to interfere with platelet function or coagulation (e.g., aspirin, ibuprofen, clopidogrel, or warfarin) unless can be discontinued for an appropriate time period based on the drug half-life and known activity (e.g., aspirin for 7 days) prior to cryoablation procedure
Use of low molecular weight heparin preparations unless can be discontinued 8 hours prior to cryoablation