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

• Status: Completed
• Trial end date: 2018-11-01
• Target enrollment: 0
• Participant gender: Female

Summary

Prospective, randomized, open label, two arms,, phase 0 clinical trial. HER2-negative breast cancer patients recently diagnosed will be screened for trial participation.

A biopsy will be scheduled the week prior to or the same day as the FDG PET. Paraffin-embedded tumor samples will be used to evaluate the stainings of Ki67, cleaved caspase-3 and microvessels, and frozen tumor samples will be used to evaluate SDH staining.

The FDG-PET will be followed by the bevacizumab dose (15 mg/kg IV, single dose). After one week, the PET will be repeated in order to detect the patients that have experienced FDG uptake decay.

Right after, treatment with ME-344 (arm 1) or no treatment (arm 2) will start. ME-344 will be administered at 10 mg/kg on day 8, 15 and 22. Surgery will be performed on day 28 (thus, 4 weeks after the bevacizumab dose, which is considered a safe window for antiangiogenics).

Fragments of the surgical specimen will be collected. Paraffin-embedded tumor sample will be used to repeat (and compare) the stainings of Ki67, cleaved caspase-3 and microvessels, and frozen tumor sample will be used to repeat (and compare) SDH staining.

Patients will come off trial in case of consent withdrawal, unequivocal disease progression is observed, unacceptable toxicity occurs, or in case of intercurrent disease or any other condition deemed incompatible with continuation in the clinical trial by the investigator.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centro Nacional de Investigaciones Oncologicas CARLOS III
• Collaborators: Fundación CRIS; Fundacion CRIS de Investigación para Vencer el Cáncer
• Treatments: Angiogenesis Inhibitors; Bevacizumab

Criteria

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.