Trial Information

Summary: The purpose of this study is to determine whether RTA 744 is effective in the treatment of breast cancer that has metastasized to the brain.

The purpose of this study is to evaluate the efficacy of RTA 744 in reducing intracranial tumor on contrast-enhanced MRI of breast cancer patients with progression of brain metastases following whole brain radiotherapy (WBRT). RTA 744 is a novel anthracycline that has shown the ability to circumvent ATP-binding cassette transporters (Multidrug Resistance Protein 1, Breast Cancer Resistance Protein, P-glycoprotein) in vitro. This Phase II study will investigate the safety and efficacy of RTA 744 in patients with breast cancer and metastatic disease to the brain which has progressed following whole brain irradiation.

CRITERIA:

Inclusion Criteria:

• Females, 18 years and older
• 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
• Definitive radiotherapy = 3000 cGy for documented CNS disease completed = 4 weeks prior to initiation of protocol therapy
• = 2 weeks since stereotactic radiosurgery or gamma knife therapy
• = 4 weeks since neurosurgery (open brain or stereotactic brain biopsy). Patients must have completely recovered from the side effects of surgical procedure.
• = 2 weeks since major surgery (other than neurosurgical procedure) and complete recovery from this surgical procedure.
• Most recent chemotherapeutic treatment regimen completed = 2 weeks prior to study entry provided toxicities have resolved.
• Life expectancy = 12 weeks.
• Patients receiving corticosteroids must have been on a stable dose for 2 weeks prior to study enrollment.
• LVEF = 50% on MUGA or ECHO
• ECOG performance status of 0-2.
• Laboratory values confirmed within 14 days of initiation of study therapy
• 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.
• Cognitive ability to provide written informed consent and comply with study requirements including follow-up procedures.

Exclusion Criteria:

• Evidence of new or progressive metastatic disease in the brainstem or intramedullary upper spinal cord. (Metastases in the thalamus are allowed).
• Evidence of diffuse leptomeningeal disease on brain MRI or by previously documented CSF cytology. (Discrete dural metastases are permitted.)
• Evidence of impending herniation on baseline MRI.
• Evidence of CNS hemorrhage on baseline MRI (within 14 days of study enrollment).
• Grade 3 or 4 motor, sensory, or cranial neuropathy symptoms; Grade 3 or 4 seizures, headache or nausea/vomiting.
• Evidence of bleeding diathesis, coagulopathy or requirement for therapeutic anticoagulation.
• Total lifetime, cumulative anthracycline dose > 350 mg/m2.
• Impaired cardiac function or other significant cardiac disease or arrhythmia of any type
• Concurrent or recent (within 4 weeks prior to randomization) medication(s) that may interfere with study treatment or results, i.e., immunosuppressants other than corticosteroids, enzyme-inducing anti-epileptics and agents that prolong the QTc.
• Concurrent or planned hormonal, chemotherapeutic, experimental, or targeted biologic therapy.
• Any of the following concurrent severe or uncontrolled medical condition which could compromise participation in the study: Uncontrolled diabetes; Active or uncontrolled infection; Acute or chronic liver disease (i.e. hepatitis, cirrhosis); Patients having a contraindication to MRI imaging
• Pregnant
• Inability to comply with study and/or follow-up procedures.

If you would like to learn more about participating in this study, please send an e-mail message using the form below.