A Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis

Inclusion Criteria:

* Histologic confirmation of primary malignancy. All primary tumor types may be enrolled.
* Neoplastic meningitis/leptomeningeal metastasis refractory to conventional therapy with presence of tumor cells on cytology, OR neuroimaging evidence of leptomeningeal tumor by MRI.
* Not eligible for higher priority clinical trial.
* Have recovered from side effects of any surgical resection.
* A stable dose of steroid for at least 7 days prior to the Gd-MRI.
* Karnofsky Performance Status (KPS) of ≥ 60.
* Laboratory Parameters: ANC ≥ 1.5 x 109/L; Hgb ≥ 9 g/dl; Platelets ≥ 100 x 109/L; AST and ALT ≤ 3.0 x ULN; Serum bilirubin ≤ 1.5 x ULN; Serum creatinine ≤ 1.5 x ULN; 24 hour creatinine clearance ≥ 50 ml/min
* Life expectancy of at least 8 weeks.
* Written informed consent obtained.

Exclusion Criteria:

* Concurrent therapy for leptomeningeal disease or other malignancy.
* Clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow.
* Cumulative doses: doxorubicin \> 450 - 550 mg/m2, epirubicin \> 800-1000 mg/m2, idarubicin \>130-150 mg/m2 and daunorubicin \> 400-550 mg/m2.
* Anticonvulsant medications or other types of medications which are known to induce the CYP450 enzymes.
* Pregnancy or breast feeding, or adults (male or female) of reproductive potential not employing an effective method of birth control
* Total 24 hour urinary protein \> 500 mg.
* Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
* Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any type
* Myocardial infarction ≤ 6 months prior
* History of CHF or arrhythmias
* Therapeutic doses of anticoagulant therapy (prophylactic dosing is allowed)
* Investigational drugs less than 4 weeks prior; intrathecal chemotherapy within 2 weeks prior; systemic cytotoxic chemotherapy within 4 weeks prior (6 weeks for nitrosourea or mitomycin-C or 2 weeks for vincristine); radiation therapy within 2 weeks prior; any medication known to cause QT interval prolongation
* Any surgery \<2 weeks prior