Repeat Radiation, Minocycline and Bevacizumab in Patients With Recurrent Glioma

After providing informed consent, patients will undergo screening for eligibility to
participate in the study. Screening will start within 21 days prior to dosing.

Subjects will have an MRI within 21 days of starting radiation. QOL and cognition measures
will be performed within 21 days of starting radiation. Radiation will be given with
parameters determined on an individual basis by the radiation oncologist. Bevacizumab will be
continued at 10mg/kg IV every 2 weeks. Minocycline will be given twice a day starting at
100mg PO bid. MRI, QOL, and cognitive tests will be obtained 1, 3 and 6 months after the end
of radiation.

Inclusion Criteria:

1. Male or female patients ≥18 years old with a life expectancy of at least 8 weeks

2. Radiographically proven recurrent (≥ first relapse), intracranial glioma

3. Previous treatment with external beam radiation

4. Radiographic progression on current or prior bevacizumab treatment

5. 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 ≥1 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.

6. Karnofsky performance status of ≥50

7. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x
109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, aspartate aminotransferase
(AST)/alanine aminotransferase (ALT) ≤2.5x ULN, creatinine ≤1.5x ULN)

8. Willing and able to provide written informed consent prior to any study related
procedures and to comply with all study requirements

9. Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days
prior to study registration

10. Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on
warfarin confirmed by testing within 14 days prior to study registration

11. Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight (LMW)
heparin) must have no active bleeding or pathological condition that carries a high
risk of bleeding, and must be on a stable dose of oral anticoagulant or on a stable
dose of low molecular weight heparin

Exclusion Criteria:

1. Use of an investigational drug within 14 days or within 5 half-lives of teh
investigational drug, whichever is shorter

2. Progression within 3 months of previous radiation by Radiographic Assessment in
Neurooncology (RANO) criteria

3. History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage

4. A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy,
radiation, adjuvant therapy).

5. Patients with serious illnesses, uncontrolled infection, medical conditions, or other
medical history including abnormal laboratory results, which in the investigator's
opinion would be likely to interfere with a patient's participation in the study, or
with the interpretation of the results

6. Women of child-bearing potential who are pregnant or breast feeding

7. Unstable angina and/or 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, evidence of recent myocardial infarction by EKG performed within 14 days
of registration, serious or inadequately controlled cardiac arrhythmia, significant
vascular and peripheral vascular disease, evidence of bleeding diathesis or
coagulopathy

8. History of stroke, cerebral vascular accident (CVA) or transient ischemic attack
within 6 months

9. Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula,
gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open
biopsy, or significant traumatic injury within 28 days prior to registration, with the
exception of the craniotomy for tumor resection

10. Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration

11. Active connective tissue disorders, such as lupus or scleroderma, that in the opinion
of the treating physician may put the patient at high risk for radiation toxicity