Alpha-TEA and Trastuzumab for the Treatment of Refractory HER2+ Metastatic Breast Cancer

This is an interventional treatment trial for Anatomic Stage IV Breast Cancer AJCC v8 focused on measuring Breast, HER2+, metastatic, refractory, immunotherapy Read More

Inclusion Criteria:

• Patients with HER2/neu overexpressing metastatic breast, not considered curable by conventional therapies

  • HER2 positivity will be defined per the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines (Journal of Clinical Oncology [JCO] 2018)
  • Extra-skeletal disease that can be accurately measured >= 10 mm by standard imaging techniques within 28 days of treatment
• Patients must continue trastuzumab with or without pertuzumab dosing per standard of care through the entire study period
• Prior lapatinib in the metastatic setting is allowed, but not required
• Patients with estrogen receptor (ER) and / or progesterone receptor (PR) positive metastatic breast cancer are eligible and may continue anti-estrogen therapy for the duration of the study
• Patients must be at least 14 days post cytotoxic chemotherapy prior to enrollment
• Patients must be at least 14 days post immunosuppressant prior to enrollment
• Patients on bisphosphonates and/or endocrine therapy are eligible and can continue on this therapy concurrently
• Women who are having sex that can lead to pregnancy must have a negative pregnancy test and must avoid becoming pregnant while on alpha-TEA and for 4 weeks after the last dose of alpha-TEA. Men must avoid fathering a child while on alpha-TEA and for 4 weeks after the last dose of alpha-TEA
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =< 2
• Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have significant active concurrent medical illnesses precluding study treatment
• White blood cell (WBC) >= 2000/mm^3 (within 28 days prior to first treatment)
• Hemoglobin (Hgb) >= 8 mg/dl (within 28 days prior to first treatment)
• Estimated creatinine clearance (Crcl) by the Cockcroft-Gault (C-G) equation >= 60 mL/min (within 28 days prior to first treatment)
• Total bilirubin =< 1.5 x upper limit of normal (within 28 days prior to first treatment)
• Aspartate aminotransferase (AST) < 1.5 X upper limit of laboratory normal (within 28 days prior to first treatment)
• Alanine aminotransferase (ALT) < 1.5 X upper limit of laboratory normal (within 28 days prior to first treatment)
• Alkaline phosphatase < 2.5 X upper limit of laboratory normal (within 28 days prior to first treatment)
• International normalized ratio (INR) < 1.5 (within 28 days prior to first treatment)
• Prothrombin time (PT) < 16 seconds (within 28 days prior to first treatment)
• Partial thromboplastin time (PTT) < 38 seconds (within 28 days prior to first treatment)
• Ability to swallow capsules
• Patients must have adequate cardiac function as demonstrated by normal left ventricular ejection fraction (LVEF) >= the lower limit of normal for the facility on multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) within 3 months of enrollment
• Must be off vitamin E supplements for at least two weeks prior to first dose of study drug

Exclusion Criteria:

• Patients with any of the following cardiac conditions:

  • Restrictive cardiomyopathy
  • Unstable angina within 6 months prior to enrollment
  • New York Heart Association functional class III-IV heart failure
  • Symptomatic pericardial effusion
  • Right atrial enlargement on ECHO would not be allowed
• History of or active atrial fibrillation or supraventricular tachycardia
• History of documented cardiac arrhythmia
• Active cardiac ischemia. Patients with a history of ischemia ameliorated with stent placement or coronary artery bypass grafting and who have no evidence of ischemia by exercise or physiological stress testing are eligible
• Patients with any clinically significant autoimmune disease requiring active treatment
• Patients receiving any concurrent systemic immunosuppressants. Patients who require brief courses of steroids to manage allergic reaction to intravenous contrast used in radiographic studies are eligible
• Patients receiving strong inhibitors or inducers of CYP3A4/5
• Patients who are pregnant or breast-feeding
• Patients who are simultaneously enrolled in other treatment studies
• Active brain metastatic disease. Patients with brain metastases who have been treated with surgery, gamma-knife radiosurgery or radiation and no radiographic progression for at least 4 weeks and off steroids are eligible
• Any medical or psychiatric condition that in the opinion of the principal investigator (PI) would preclude compliance with study procedures
• Malabsorption state such as ulcerative colitis, previous surgical resection of > 20% of intestine or stomach
• Surgery or severe trauma within 4 weeks of study entry (minimally invasive procedures acceptable)
• Corrected QT interval (QTc) greater than 450 msec at (calculated using Bazett's formula), sick-sinus syndrome or other active cardiac disease
• Patient with abnormal thyroid function or who are euthyroid but on medication for thyroid disorders must be excluded