RTA 744 in Breast Cancer Patients With Progression of Previously Irradiated Brain Metastases

Inclusion Criteria

• •1. Histologically-confirmed adenocarcinoma of the breast with at least one evaluable brain lesion ( ≥ 1 cm in one dimension) on contrast-enhanced MRI after WBRT and documented intracranial failure/progression i. Presence of any new lesion(s); or ii. ≥ 25% increase in bi-dimensional measurement of existing tumor
• •2. Definitive radiotherapy ≥ 3000 cGy for documented CNS disease completed ≥ 4 weeks prior to initiation of protocol therapy
• •3. ≥ 2 weeks since stereotactic radiosurgery or gamma knife therapy
• •4. ≥ 4 weeks since neurosurgery (open brain or stereotactic brain biopsy). Patients must have completely recovered from the side effects of surgical procedure.
• •5. ≥ 2 weeks since major surgery (other than neurosurgical procedure) and complete recovery from this surgical procedure.
• •6. Most recent chemotherapeutic treatment regimen completed ≥ 2 weeks prior to study entry provided toxicities have resolved.
• •i. Hormone receptor positive patients must have progressed on one prior hormonal AND at least one prior chemotherapy course in the metastatic setting.
• •ii. Hormone receptor negative patients must have progressed on at least one prior chemotherapy course in the metastatic setting.
• •iii. Her2 positive patients must have progressed on at least one prior chemotherapeutic and one Her2-targeted combination course in the metastatic setting.
• •7. Life expectancy ≥ 12 weeks.
• •8. Patients receiving corticosteroids must have been on a stable dose for 2 weeks prior to study enrollment.
• •9. LVEF ≥ 50% on MUGA or ECHO
• •10. ECOG performance status of 0-2.
• •11. Laboratory values confirmed within 14 days of initiation of study therapy: Granulocytes ≥ 1,500/μL; Lymphocytes ≥ 1,000/μL; Platelets ≥ 100,000/μL; Hemoglobin ≥ 9 gm/dL; Total Bilirubin \< 1.5 times upper limit of normal (ULN); ALT and AST \< 1.5 times ULN (\< 5 times ULN in patients with liver metastases); Creatinine \< 1.5 times ULN
• •12. Women of childbearing potential must have negative serum pregnancy test, and must agree to use adequate contraceptive method during administration of study treatment and for three months after completing treatment.
• •13. Cognitive ability to provide written informed consent and comply with study requirements including follow-up procedures.