Phase I Newly Diagnosed GBM With Temozolomide, Radiation, and Minocycline Followed by Adjuvant Minocycline/Temozolomide (D-TERMINED)

Inclusion Criteria:

Male or female patients greater than or equal to 18 years old Histopathologically proven diagnosis of glioblastoma (GBM) or gliosarcoma or anaplastic astrocytoma(AA) A diagnostic contrast-enhanced MRI or CT scan of the brain must be performed preoperatively and postoperatively (preferably within 96 hours of surgery), prior to the initiation of radiotherapy. The post-operative MRI must be within 35 days prior to study registration.

Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and post-operative contrast-enhanced CT scans are obtained and are of sufficient quality.

Radiation therapy planned to start less than or equal to 6 weeks after surgery and at least 7 days after the start of minocycline Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for greater than or equal to1 year. Men of child-bearing potential must also agree to use an acceptable method of birth control while on study drug, and for 3 months after the last dose.

Karnofsky performance status of greater than or equal to 70 Adequate bone marrow function, coagulation, hepatic, and renal function as defined by lab testing.

Exclusion Criteria:

Prior radiation or chemotherapy for high grade glioma Prior invasive cancer (except nonmelanoma skin cancer) unless disease free for at least 2 years or life expectancy without treatment is greater than 2 years, e.g., low risk localized prostate cancer.

Prior radiation to the head or neck with overlapping radiation fields Patients who had a stereotactic needle biopsy Unstable angina and/or decompensated congestive heart failure in the last 6 months, transmural myocardial infarction within the last 6 months, New York Heart Association grade II or higher congestive heart failure requiring hospitalization within 12 months prior to registration, serious or inadequately controlled cardiac arrhythmia, significant vascular and peripheral vascular disease, evidence of bleeding diathesis or coagulopathy.

History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis Acquired immune deficiency syndrome (AIDS) based upon current CDC definition or known HIV seropositivity; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with HIV/AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.

Active connective tissue disorders, such as lupus or scleroderma Patients with history of allergic reaction to minocycline or to any of the tetracyclines Patients with history of erosive esophagitis should be excluded from the study Patients that are on anticonvulsant medications would be switched, when possible, to a non-enzyme-inducing antiepileptic drug (non-EIAED). However, if that is not possible, they will not be excluded from the study.

Other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy Women who are breast feeding, due to possible adverse effects on the infant Prior allergic reaction to temozolomide