Whole Brain Radiation Therapy With Standard Temozolomide Chemo-Radiotherapy and Plerixafor in Treating Patients With Glioblastoma

PRIMARY OBJECTIVES:

I. To assess the 6 month progression-free survival (PFS) (post initiation of radiation) of
continuous infusion plerixafor beginning one week prior to the end of concurrent chemotherapy
with temozolomide and a modified radiation regimen that includes a component of whole brain
radiation therapy (WBRT) in patients with newly diagnosed glioblastoma (GBM).

SECONDARY OBJECTIVES:

I. To assess the median survival of patients treated with continuous infusion
plerixafor/WBRT.

II. To assess the toxicities both short and long term of continuous infusion plerixafor/WBRT.

III. To assess the patterns of failure (in and out of irradiated brain field, out of brain)
of continuous infusion plerixafor/WBRT.

OUTLINE:

After completion maximal safe surgical resection, patients undergo radiation therapy for 42
days, initiating whole brain radiation therapy at day 21 (dose 16 of radiation therapy) and
receive temozolomide daily on days 1-42. Beginning 7 days before the completion of whole
brain radiation therapy, patients receive plerixafor by continuous infusion on days 1-28.
Beginning 1 week after completion of plerixafor infusion and 35 days after completion of
whole brain radiation therapy, patients receive temozolomide monthly for 6-12 courses in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for adverse events for 30 days
after the last dose of Plerixafor and then every 12 weeks for 5 years for survival follow-up.

Inclusion Criteria:

- Patients must have tissue confirmation of high grade (World Health Organization (WHO)
grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma
with oligodendroglial features, glioblastoma with primitive neuroectodermal tumor
(PNET) features.

- The patient must have post-operative contrast enhanced imaging (computed tomography
[CT] or magnetic resonance imaging [MRI]) unless only biopsy performed. For patients
having biopsy alone, post-operative imaging is not routinely obtained and therefore
the preoperative study will serve as baseline.

- Patient should have surgery (biopsy, partial resection or gross total resection) and
no additional anti-cancer therapy except the chemo-radiation as specified in the
protocol.

- Patients must have Karnofsky performance score >= 60.

- Absolute neutrophil count (ANC) >= 1500 (at time of screening).

- Platelets >= 100,000 ml (at time of screening).

- Serum creatinine =< 1.5mg/dl (at time of screening).

- Creatinine (Cr) clearance should be > 50 mL/min (at time of screening).

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times the
upper limit of normal (at time of screening).

- If female of childbearing potential, negative pregnancy test (at time of screening).

- The patient or his/her legal representative must have the ability to understand and
willingness to sign a written informed consent document.

- Patient agrees to use an effective method of contraception (hormonal or two barrier
methods) while on study and for at least 3 months following the plerixafor infusion.

Exclusion Criteria:

- Prior or concurrent treatment with Avastin (bevacizumab).

- Prior exposure to plerixafor.

- Prior use of other investigational agents to treat the brain tumor.

- Recent history of myocardial infarct (less than 3 months) or history of active angina.

- Prior malignancy except for non-melanoma skin cancer and carcinoma in situ (of the
cervix or bladder), unless diagnosed and definitively treated more than 3 years prior
to 1st dose of investigational drug.

- Prior sensitivity to plerixafor.

- Pregnant or patients who are breastfeeding.