Patient case: 35-year-old female with Breast cancer. Genetic variant: NRAS Amplification. Other conditions: None.

Clinical trial: Fresolimumab and Radiotherapy in 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: 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.

Relevance to patient case: not relevant