Intervention: Temozolomide
Trial phase: Phase 1 | Phase 2
ATC code: L01AX03
SMILES: Cn1nnc2c(C(N)=O)ncn2c1=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 12
Group description: Patients will undergo an induction phase of intraventricular (ITV) DepoCyt, using the dosage determined from the Phase I portionPatients with stable disease (clinically and radiographically), not exhibiting systemic toxicity, will undergo a three month consolidation phase of ITV DepoCyt, for one month (Cycles 3-6). Patients without progression or toxicity will undergo maintenance therapy using ITV DepoCyt every four weeks (+/- 3 days) for a maximum of 8 months (cycles 7-14) or until recurrence or toxicity ensues.

ITV DepoCyt + Temozolomide: Intrathecal liposomal Ara-C dosing will begin at 50 mg ITV every 2-4 weeks, and de-escalated based on toxicity obtained from the Phase I portion of the trial. Metronomic dosing of temozolomide will be given at 75 mg/m2 for 21 days (continuous ora
Eligibility criteria:
Inclusion Criteria:

Age Patients must be at least 18 years of age but no older than 85 years.
Diagnosis Patients with the histological diagnosis of recurrent GBM made either by biopsy or resection of recurrent disease. Cytological evidence of malignant cells in CSF and/or clinical and radiographic evidence of leptomeningeal disease are irrelevant in terms of inclusion or exclusion into this study. Bihemispheric extension ("butterfly GBM"), multi-focality, and/or subependymal spread are not contraindications to enrollment.
Prior therapy Patients must have had an initial diagnosis of "malignant glioma" (WHO grade III or IV) and failed initial surgical resection followed by standard adjuvant therapy including external beam radiotherapy to a 2cm margin of 60 Gy, and standard temozolomide chemotherapy of 150 to 200 mg per square meter for 5 days during each 28-day cycle prior to "recurrence." Patients must not have received more than one other systemic or ITV adjuvant chemotherapy regimen in addition to temozolomide prior to enrollment, not including intracavitary Gliadel wafer placement. Prior Gliadel wafer placement is not a contradiction to patient enrollment in this trial.
Performance Status Patients must have Karnofsky performance status (KPS) of ≥ 60%.
Recovery from Prior Therapy Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, prior to entering this study and must be without significant systemic illness (e.g. infection unresponsive to treatment after 7 days). Such that they are healthy enough to safely undergo tumor biopsy and Ommaya reservoir placement. Patients must not have received any systemic therapy for recurrent disease within 3 weeks (6 weeks if a nitrosourea), or irradiation within 8 weeks prior to treatment on this study.
Hematologic Status Patients must have a platelet count > 75,000/mm3 and ANC > 1500/mm3 within 72 hours prior to ITV DepoCyt treatment.
Hepatic and Renal Status Patients must have adequate liver function (total bilirubin < 2.0 mg%; ALT, and AST < 4 times normal); adequate renal function (serum creatinine <1.6 mg, and BUN < 22); normal serum electrolytes (sodium, potassium, calcium, magnesium, and phosphorus).
Informed Consent (See Appendix) All patients or their legal guardians must sign a document of informed consent indicating their awareness of the investigational nature and the risks of this study.

Exclusion Criteria:

Patients younger than 18 or older than 85 years of age.
Patients with histological diagnoses other than recurrent GBM.
Patients with a Karnofsky performance status (KPS) < 60%.
Patients that have received more than one other systemic or ITV adjuvant chemotherapy regimen in addition to temozolomide, not including intracavitary Gliadel wafer placement.
Patients concurrently receiving other therapies (either brachytherapy or systemic) designed specifically to treat the recurrent GBM.
Patients within 8 weeks of receiving stereotactic or external beam irradiation.
Patients with a platelet count < 75,000/mm3 and ANC < 1500/mm3 within 72 hours prior to ITV DepoCyt and/or oral temozolomide treatment.
Patients with liver dysfunction (total bilirubin > 2.0 mg%; ALT, and AST > 4 times normal).
Patients with renal dysfunction (serum creatinine >1.6 mg, and BUN > 22).
Patients with abnormal serum electrolytes (sodium, potassium, calcium, magnesium, and phosphorus).
Patients with contraindications to having placement of a ventricular access device such as Ommaya reservoir.
Patients with clinical and/or neuroradiographic evidence of hydrocephalus or increased intracranial pressure.
Patients with signs and symptoms of systemic infection precluding them from receiving chemotherapy or prohibiting Ommaya reservoir placement.
Pregnant and breast feeding women will be excluded. All other women of childbearing years must have a negative serum pregnancy test.
Patients with a ventricular-peritoneal or ventricular-atrial shunt.
Prisoners will be excluded from this study.
Patients or their legal guardians not willing or able to sign the informed consent document.