Tremelimumab and Durvalumab in Combination or Alone in Treating Patients With Recurrent Malignant Glioma

Inclusion Criteria

• Patients must have a grade III or IV glioma that has progressed after standard radiotherapy (RT) and temozolomide (TMZ) (Note: Pathology will need to be reviewed locally but registration can occur based on pathology report)
• Patients must have had radiographic evidence of tumor progression by brain MRI or computed tomography (CT) scan with contrast
• Patients must be > 12 weeks from completion of radiation therapy unless there is tissue confirmation of tumor recurrence or there is progression outside the radiation treatment field
• Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence occurs remote from the treated site
• Patients must be surgical candidates
• Patients must have had no more than 3 prior lines of chemotherapy; this includes the initial treatment and two relapses; concurrent and adjuvant TMZ-based chemotherapy, including the combination of TMZ with another agent, is considered one line of chemotherapy; for clarification, please contact the principle investigator (PI), Dr. Jeffrey Raizer, at (312) 695-0990
• Patients must be >=
• 4 weeks from TMZ
• 6 weeks from a nitrosoureas
• 3 weeks from a biologic or targeted agent (i.e. small molecule)
• 4 weeks for a vascular endothelial growth factor (VEGF) inhibitor (i.e. bevacizumab)
• Patients must exhibit a Karnofsky performance status (KPS) >= 70
• Life expectancy of >= 12 weeks (per treating investigator's discretion)
• Patients must be on a stable or decreasing dose of corticosteroids within 5 days prior to CT scan or MRI (which is done to determine eligibility); the goal should be dexamethasone 4 mg or less at the time of starting treatment; if patient requires > 4mg of steroid, please check with the principle investigator (PI); requirement for greater than 10mg of steroid will make the patient ineligible
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcl
• Hemoglobin (Hb) > 10.0 g/dL (can be transfused to this level)
• International Normalized Ratio (INR), prothrombin time (PT), or activated partial thromboplastin time (aPTT) as follows:
• In the absence of therapeutic intent to anticoagulate the patient: INR 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
• Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (e.g. hormonal or barrier method of birth control prior to registration, for the duration of study participation, and for 180 days after the last dose of MEDI4736 + tremelimumab combination therapy or 90 days after the last dose of MEDI4736 or tremelimumab monotherapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets both of the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy
• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
• FOCBP must have a negative pregnancy test (serum or urine) within 7 days prior to registration on study
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Malignancy treated with curative intent and with no known active disease >=3 years before the first dose of study drug and of low potential risk for recurrence; NOTE: the exceptions to this requirement include adequately treated non-melanoma