ME-344 in Early HER2-negative Breast Cancer With Antiangiogenic-induced Mitochondrial Metabolism

Inclusion Criteria:

1. Women older than 18 year-old.
2. Treatment-naïve diagnosed early (stage I-III) HER2-negative (histologically confirmed) breast cancer not candidates for neoadjuvant therapy.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Signed informed consent obtained from the subject prior to performing any protocol-related procedures.
5. Negative pregnancy test, or confirmed menopause.
6. Adequate organ function, according to the following parameters:

   * Haemoglobin ≥ 9.0 g/dL.
   * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 / mm3).
   * Platelet count ≥ 100 x 109/L (\>100000 / mm3).
   * Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
   * AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal.
   * Serum creatinine \< 1.5 x institutional upper limit of normal (ULN).
7. Cardiac ejection fraction above 45%.
8. Life expectancy superior to 6 months.
9. Willingness to undergo trial procedures.

Exclusion Criteria:

1. Neuropathy of any kind.
2. Diabetes mellitus.
3. Presence of intercurrent uncontrolled diseases, including untreated hypertension.
4. Participation in another clinical study with an investigational product during the last 4 weeks.
5. Patients with presence of concurrent or active malignant disease (other than disease under study) within the last 12 months with the exception of adequately treated in situ carcinomas, basal or squamous cell carcinoma, or nonmelanomatous skin cancer.
6. Female subjects who are pregnant, breast-feeding or of reproductive potential who are not employing an effective method of birth control.
7. Uncontrolled infection or systemic disease.
8. Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months.
9. No concurrent systemic chemotherapy or biologic therapy is allowed.
10. Known hypersensitivity to any components of ME-344 or bevacizumab.
11. Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both).
12. History of solid organ transplantation.
13. Psychiatric disorder or social or geographic situation that would preclude study participation.
14. Inability to comply with the study and follow-up procedures (e.g. tumor biopsies).
15. Any other condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.