This phase II trial studies how well whole brain radiation therapy works with standard temozolomide chemo-radiotherapy and plerixafor in treating patients with glioblastoma (brain tumor). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Plerixafor is a drug that may prevent recurrence of glioblastoma after radiation treatment. Giving whole brain radiation therapy with standard temozolomide chemo-radiotherapy and plerixafor may work better in treating patients with glioblastoma.

PRIMARY OBJECTIVES:

I. The primary purpose of this Phase II study is to evaluate the efficacy of Plerixafor administered with a modified radiation regimen that includes a component of WBRT. The primary endpoint is 6-month progression free survival post initiation of Chemoradiation.

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.