Fresolimumab and Radiotherapy in Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Fresolimumab; Radiation Therapy
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic breast cancer; TGF-beta; fresolimumab; monoclonal antibody; radiation therapy; abscopal response

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.