Plerixafor After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed High Grade Glioma

Study Overview
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Brief Summary
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This pilot phase I/II trial studies the side effects and best dose of plerixafor after radiation therapy and temozolomide and to see how well it works in treating patients with newly diagnosed high grade glioma. Plerixafor may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill tumor cells. Giving plerixafor after radiation therapy and temozolomide may be an effective treatment for high grade glioma.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the safety of using continuous infusion Plerixafor subsequent to irradiation in patients with newly diagnosed glioblastoma multiforme (GBM). II. To assess the efficacy of Plerixafor as measured by progression free survival at 6 months (PFS6) from the start of irradiation. OUTLINE: This is a phase I, dose-escalation study of plerixafor followed by a phase II study. Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide orally (PO) over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor intravenously (IV) continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy. After completion of study treatment, patients are followed up every 12 weeks for 5 years.

Official Title
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A Phase I/II Study of Local Field Irradiation and Temozolomide Followed by Continuous Infusion Plerixafor as an Upfront Therapy for Newly Diagnosed Glioblastoma GBM

Conditions
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Adult Ependymoblastoma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Medulloblastoma, Adult Mixed Glioma, Adult Oligodendroglial Tumors, Adult Pineoblastoma, Adult Supratentorial Primitive Neuroectodermal Tumor (PNET)

Intervention / Treatment
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* Radiation: radiation therapy
* Drug: temozolomide
* Drug: plerixafor
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have tissue confirmation of high grade (WHO Grade IV) glioma including but not limited to glioblastoma, gliosarcoma, glioblastoma with oligodendroglial features, glioblastoma with PNET features. The patient must have post-operative contrast enhanced imaging (CT or MRI) unless only biopsy performed (in which case post-operative imaging is not routinely obtained. In these patients, 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 chemoradiation as specified in the protocol. For those patients in which steroids are clinically indicated, there must be a stable or decreasing dose of steroid medication for ≥ one week prior to the start of infusion. Patients must be between the ages of 18 and 75 years old. Patients must have Karnofsky Performance score ≥ 60. Adequate organ function is needed at time of screening visit including: ANC ≥ 1500 Platelets ≥ 100,000 ml Serum Creatinine ≤ 1.5mg/dl; Cr Clearance should be >50 mL/min AST and ALT ≤ 3 times the upper limit of normal If female of childbearing potential, negative pregnancy test 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 or arrhythmia Prior malignancy except previously diagnosed and definitively treated more than 3 years prior to trial or whose prognosis is deemed good enough to not warrant surveillance Prior sensitivity to Plerixafor Pregnant or patients who are breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (radiation therapy, temozolomide, plerixafor)<br>Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide PO over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor IV continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy. | Radiation: radiation therapy<br>* Undergo radiation therapy<br>* Other names: therapy, radiation;Drug: temozolomide<br>* Given PO<br>* Other names: TMZ;Drug: plerixafor<br>* Given IV<br>* Other names: Mozobil;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting Toxicity | Dose Limiting Toxicity is defined as defined as any hematologic or on-hematologic adverse events grade 3 or higher using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 with a suspected causal relationship to Plerixafor (including electrocardiogram changes indicative of ischemia, ventricular tachycardia) | Up to 30 days post plerixafor | 
| Participants Alive and Without Disease Progression At 6 Months After the Start of the Irradiation | Progression free survival based on the Response Assessment for Neuro-Oncology (RANO) criteria, using both clinical examinations and MRIs with and without contrast summarized with Kaplan Meier estimates. | 6 months from start of irradiation |