Phase I Trial Of Temozolomide Combined With The Histone Deacetylase Inhibitor Valproic Acid (VPA) And Whole Brain Radiation Therapy (WBR) For Brain Metastases From Solid Tumors In Adults

Inclusion Criteria:

- Patients must have cytologically/histologically documented solid tumor malignancies

- Age > 18 years old

- Patients must be candidates to receive WBR for unresectable brain metastases

- Patients must have ECOG performance status 0-2

- Patients must be able to give informed consent and able to follow guidelines given in
the study

- Neurologic Function Status 0,1, or 2

- The patient has no major impairment of hematological function, as defined by the
following laboratory parameters: WBC >3.0x109/L; ANC > 1.5 x 109/L; Hgb >9.0g/dL; PLT
>100x109/L. Red blood cell transfusions and repeat evaluations for study entry are
allowed

- Patients must have adequate renal and normal hepatic function (creatinine < 1.5 x
upper limit of normal (ULN), bilirubin and SGOT (AST), SGPT (ALT) within 1.5 x the
upper institutional normal limits) obtained within 4 weeks prior to registration.

- All patients of reproductive potential must use an effective method of contraception
during the study and six months following termination of treatment. (Not applicable
to patients with bilateral oophorectomy and/or hysterectomy or to female patients who
are older than 50 years and have not had a menstrual cycle in more than one year).

- Women of childbearing age must have a negative pregnancy test

- Patients must have 10 mm or greater brain lesion on MRI scan performed within 4 weeks
of enrollment

Exclusion Criteria:

- Prior whole brain radiation

- More than 1 active malignancy which may potentially cause brain metastasis

- Patients on phenytoin, carbamazepine, phenobarbital, felbamate, meropenem, rifampin
(Levetiracetam will be permitted)

- Patients with active or any history of seizure disorders

- Patients with uncontrolled nausea and vomiting

- Chemotherapy, radiotherapy, or hormonal therapy within 2 weeks prior to entering the
study or have not recovered from prior treatment-related toxicities (grade 2 or less)

- Patients receiving any other investigational agents

- Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess,
etc.) at time of study entry.

- Leptomeningeal disease or hydrocephalous on MRI scan performed within 4 weeks of
enrollment

- Pregnant and breast feeding women are excluded from the study because effects on the
fetus are unknown and there may be a risk of increased fetal wastage.