A Phase 0/1 Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination With Standard Therapy in Recurrent High Grade Gliomas

Inclusion Criteria 1. Radiographically, histologically or cytologically confirmed recurrent brain high grade glioma with plan for resection or biopsy. \- Inclusion #1 for Sub-study Only: Radiographically, histologically or cytologically confirmed recurrent brain high grade glioma. 2. Age \>18 years. 3. ECOG performance status 0 -2 (Karnofsky \>60%, see Appendix A). 4. CBC/differential obtained within 28 days prior to registration on study, with adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3; * Platelets ≥ 100,000 cells/mm3; * Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable). 5. Adequate hepatic function, defined as follows: * Total bilirubin \< 2 x institutional ULN within 14 days prior to registration; * AST or ALT \< 3 x institutional ULN within 14 days prior to registration. 6. Adequate renal function, defined as GFR \> 30 ml/min or Cr \< 1.5. 7. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential. 8. Imaging prior to treatment including MRI of brain (with contrast preferred but not required). 9. Ability to understand and the willingness to sign a written informed consent document. 10. Inclusion #10 for Sub-study Only: Measurable disease per RANO criteria within 28 days of starting treatment on this study. Exclusion Criteria 1. Patients may not be receiving any other investigational agents. 2. History of allergic reactions attributed to letrozole or other agents used in study. Exclusion #2 for Sub-study Only: History of allergic reactions attributed to letrozole or TMZ. 3. Uncontrolled intercurrent illness including, but not limited to, ongoing significant or serious active cardiovascular disease (CHF exacerbation, unstable angina or MI in last 6 months), or infection including the diagnosis of AIDS or active hepatitis B or C infection, or psychiatric illness or medical or personal conditions that in the opinion of the investigator would limit the patient's ability to participate. 4. Patients attempting to conceive, and pregnant or nursing women are excluded from this study.