This study will test an investigational drug called AZD1390 in combination with radiation therapy for the treatment of brain tumors. This is the first time AZD1390 is being given to patients. This study will test safety, tolerability and PK (how the drug is absorbed, distributed and eliminated) of ascending doses of AZD1390 in combination with distinct regimens of radiation therapy
Provision of formalin-fixed paraffin embedded tissue sample from primary or metastatic disease
Karnofsky Performance Score of ≥60.
Histologically proven diagnosis of GBM. Patients who have had RT for low-grade glioma (LGG) or grade 3 glioma and have subsequently relapsed to histologically confirmed GBM can be considered
A radiological diagnosis of recurrent/relapsed or progressive disease according to RANO criteria.
Administration of chemotherapy or any investigational drug in the 28 days or carmustine (CCNU) or lomustine (BCNU) in the 6 weeks prior to receiving the first dose of treatment in Arms A and C. Administration of checkpoint inhibitors within 28 days prior to first dose of treatment and any other agent within 7 days of beginning study treatment in Arm B. Hormonal therapies are allowed during study treatment for patients in Arm B.
History of severe brain-injury or stroke.
Patient not eligible for sequential MRI evaluations are not eligible for this study.
History of epileptic disorder or any seizure history unrelated to tumor