Study of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases

Inclusion Criteria

• Patients requiring a 3 week course of fractionated whole brain radiation therapy for brain metastases.
• Age > or = 18
• Histological or cytological diagnosis of a malignancy.
• Patients who have only 1-3 metastases are frequently treated with stereotactic radiation. Nonetheless, if the treating physician decides that whole brain radiotherapy is the appropriate treatment such patients would be eligible to enroll upon in the study.
• Radiographic evidence of brain metastasis.
• Measurable disease preferred but not required for eligibility
• Patient must have performance status of or = 3 months
• Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI CTCAE Version 3.0 grade or = 1500/µL
• Platelets > or = 100,000/µL
• Hemoglobin > or = 9.0 g/dL
• Serum calcium or = 2 years, surgically sterilized, or willing to use 2 adequate barrier methods of contraception to prevent pregnancy, starting with Visit 1.
• Male patient agrees to use an adequate method of contraception for the duration of the study.
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
• INR class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• An extended QTc interval on baseline EKG examination. Normal values: male 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Active clinically serious infection > CTCAE Grade 2
• NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event > or = CTCAE Grade 2 within 4 weeks of first dose of study drug.
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis or coagulopathy
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
• Use of St. John's Wort or rifampin (rifampicin).
• Any condition that impairs patient's ability to swallow whole pills.
• Any malabsorption problem.
• Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
• Documented history of cranial hemorrhage
• Patient has an active infection or has received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug.
• Patient has uncontrolled inter-current illness or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric conditions.
• Patient has a history or current evidence of any condition, ther