Open-label, Single Arm, Safety and Tolerability Dose Escalation Study of VAL-083 in Patients With Recurrent Malignant Glioma or Progressive Secondary Brain Tumor

Inclusion Criteria:

- Patients must be greater than or equal to 18 years old.

- Histologically confirmed initial diagnosis of primary WHO Grade IV malignant glioma
(glioblastoma), now recurrent, or progressive secondary brain tumor, has failed
standard brain radiotherapy, and has brain tumor progression after at least one line
of systemic therapy.

- If GBM, previously treated for GBM with surgery and/or radiation, if appropriate, and
must have failed both bevacizumab (Avastin) and temozolomide (Temodar), unless either
or both are contraindicated.

- If GBM, greater than or equal to 12 weeks from radiotherapy, or 4 weeks if a new
lesion, relative to the pre-radiation MRI, develops that is outside the primary
radiation field.

- Patients with secondary brain tumors must be greater than or equal to 4 weeks from
radiotherapy.

- At least 4 weeks from last chemotherapy or bevacizumab (Avastin) therapy (6 weeks
for nitrosourea or mitomycin C), or for chemotherapy regimes given continuously or on
a weekly basis with limited potential for delayed toxicity, at least 2 weeks from
last dose.

- Recovered from all treatment-related toxicities to Grade 1 or less.

- Must have a predicted life expectancy of at least 12 weeks.

Exclusion Criteria:

- Current history of neoplasm other than the entry diagnosis. Patients with previous
cancers treated and cured with local therapy alone may be considered with approval of
the Medical Monitor.

- Evidence of leptomeningeal spread of disease.

- Prior treatment with prolifeprospan 20 with carmustine wafer (Gliadel wafer) within
60 days prior to first treatment (Day 0).

- Prior intracerebral agents.

- Evidence of recent hemorrhage on baseline MRI of the brain.

- Concurrent severe, intercurrent illness.

- History of severe cardiac disease.

- Significant vascular disease.

- History of stroke or transient ischemic attack within 6 months prior to beginning
treatment.

- Concomitant medications that are known inducers of CYP.

- Concomitant medications that are strong inhibitors of cytochrome P450 and CYP3A up to
14 days before Cycle 1 Day 1 (pimozide, diltiazem, erythromycin, clarithromycin, and
quinidine, and amiodarone up to 90 days before)

- Pregnant or breast feeding.