Evaluation of the Efficacy and Safety of Nal-IRI for Progressing Brain Metastases in Breast Cancer Patients

Exclusion Criteria

• •1. Patients must not have previously received nal-IRI or any other form of irinotecan, conventional or liposomal.
• •2. Patients who have received prior anti-cancer treatment with chemotherapy, endocrine therapy, immunotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to starting study treatment.
• •3. Radiation therapy encompassing more than 30% of bone marrow.
• •4. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (i.e Crohn's disease, ulcerative colitis, malabsorption, or grade ≥ 2 diarrhea of any etiology at baseline)
• •5. Have a serious concomitant systemic disorder (e.g. active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or treatment with Sintrom.
• •6. Patients who have symptomatic lymphangitis, dyspnoea at rest or meningeal carcinomatosis. (Patients with asymptomatic involvement may be enrolled in the study.)
• •7. Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy or other therapy intended for the treatment of breast cancer. For peripheral neuropathy, up to CTCAE (v4.0) Grade 2 is acceptable for patients with pre-existing condition.
• •8. Patients may not be receiving any other investigational or anticancer agents while on the study.
• •9. History of other malignancies, which could affect compliance with the protocol or interpretation of the results. Patients with malignancies diagnosed more than 5 years prior to study day 1, adequately treated carcinoma in situ of the cervix or basal or squamous cell skin are generally eligible.
• •10. Pregnant or lactating women.
• •11. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings.
• •12. Active infection or an unexplained fever \>38.5°C (excluding tumoral fever), which in the physician's opinion might compromise the patient's health.
• •13. Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
• •14. Current use or any use in the last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
• •15. Known hypersensitivity to any of the components of nanoliposomal irinotecan (nal-IRI) other liposomal irinotecan formulations or irinotecan.