Mycophenolate Mofetil Combined With Radiation Therapy in Glioblastoma

Inclusion Criteria:

* Glioblastoma or gliosarcoma (recurrent or newly diagnosed).
* Karnofsky Performance Status 60 or greater.
* Phase 0: Candidate for clinically indicated re-resection or biopsy of glioblastoma or gliosarcoma per treating physician(s).
* Phase 1, Recurrent: Candidate for clinically indicated re-irradiation of glioblastoma or gliosarcoma per treating physician(s) (No more than one prior course of radiation for GBM).
* Phase 1, Newly Diagnosed: Candidate for upfront standard of care chemoradiation for glioblastoma or gliosarcoma per treating physician(s), to start no earlier than 14 days post- operatively from last definitive surgery for glioblastoma or gliosarcoma (if more than one surgery done. Ex. biopsy prior to resection).
* ANC \>=1,500 cells/mm\^3 within 14 days prior to enrollment.
* Patient (men and childbearing age women) agrees to the use of highly effective contraception during study participation and for at least 6 weeks for female patients and 90 days for male patients after final MMF administration.
* Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

* Lack of histopathological diagnosis of the tumor.
* Gliomatosis cerebri pattern (tumor involving 3 or more lobes) of disease.
* Leptomeningeal disease.
* Use of bevacizumab within 8 weeks of study enrollment.
* Known history of HIV.
* Active hepatitis B or C infection.
* Active systemic or central nervous system (CNS) infection.
* Grade 4 lymphopenia (if ALC \<0.5, patient must be on Pneumocystis jirovecii prophylaxis).
* Estimated CrCl \< 25 ml/min.
* History of organ transplantation.
* Patients with known hypoxanthine-guanine phosphoribosyl-transferase deficiency.
* Serious intercurrent disease.
* History of allergic reaction or hypersensitivity to mycophenolate mofetil or mycophenolic acid or any component of the drug product; or medical contraindication for MMF per treating physician(s).
* Known immunosuppressive condition from autoimmune disease, immune deficiency syndrome, or chronic immunosuppressive therapy.
* Inability to undergo MRI brain with and without contrast.
* Pregnant or lactating women.
* Patients with known phenylketonuria.
* Phase 0: Patients undergoing biopsy who are deemed unlikely to have sufficient tissue to spare for research purposes (e.g., those whose tumors are in an eloquent brain location where all tissue taken must be used for diagnostic purposes).
* Phase I: Increase in steroid requirement within 7 days of study enrollment (stable or decreasing dose allowed).
* Phase I, Recurrent: Radiation within 6 months prior to study enrollment.
* Phase I, Recurrent: Surgery within 4 weeks of re-irradiation.
* Phase I, Newly Diagnosed: History of hypersensitivity reactions to temozolomide or any other ingredients in temozolomide and dacarbazine.
* Phase I, Newly Diagnosed: Prior chemotherapy or radiation therapy for glioblastoma or gliosarcoma.