Phase I Trial of DNA-PK Inhibitor (M3814) in Combination With Radiation and Adjuvant Temozolomide in Newly Diagnosed MGMT Unmethylated Glioblastoma
This phase I trial investigates the side effects and best dose of Peposertib, and to see how well it works in combination with radiation therapy in treating patients with newly diagnosed MGMT unmethylated glioblastoma or gliosarcoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Peposertib may further stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Peposertib with radiation therapy may work better than radiation therapy alone in treating patients with glioblastoma or gliosarcoma.
• Signed informed consent form (ICF)
• Ability and willingness to comply with the requirement of the study protocol
• Histologically confirmed World Health Organization (WHO) grade IV glioma (GBM) or gliosarcoma, IDH wild-type
• Documentation of MGMT unmethylated GBM per testing at any Clinical Laboratory Improvement Amendment (CLIA) certified laboratory
• Patients must have undergone brain surgery or biopsy and must not have had any further treatments following surgery
• Have Karnofsky performance status (KPS) of \>= 60 or Eastern Cooperative Oncology Group (ECOG) =\< 2
• A baseline magnetic resonance imaging (MRI) of brain obtained no more than 14 days prior to study enrollment on a stable or tapering dose of steroids no greater than 4 mg a day of dexamethasone (or equivalent dose of other steroids) for at least 3 days
• Patients must start treatment within 8 weeks of last brain surgical procedure (biopsy or resection)
• Absolute neutrophil count (ANC) \>= 1,500 /mcL (within 14 days prior to day 1 of the study)
• Platelets \>= 100,000/mcL (within 14 days prior to day 1 of the study)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 14 days prior to day 1 of the study)
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (within 14 days prior to day 1 of the study)
• o Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN (within 14 days prior to day 1 of the study)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (within 14 days prior to day 1 of the study)
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN (within 14 days prior to day 1 of the study)
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (within 14 days prior to day 1 of the study)
• Have provided tissue from an archival tissue sample
• Female subjects of childbearing potential should have a negative serum pregnancy test within 14 days of day 1 of the study
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile
• o Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
• Male subjects should agree to use an adequate method of contraception during the course of the study
• STAGE I: In the case stage I patients need resection as determined by the treating physicians during or after completion of radiation therapy (RT) and that pathology of resected lesion is not consistent with recurrent GBM, the patient can continue on the study (complete 6 weeks of RT + M3814) if deemed appropriate by the treating physicians. The tissue obtained in such circumstances will be analyzed as in Stage II subjects. However, these cases will not count towards the 5 patients who will be enrolled during Stage II. These patients will contribute to the correlative endpoints detailed above and ORR, OS, and PFS as Stage II patients
• STAGE II: Patients meet above criteria, would benefit from further non-urgent surgical resection of at least one enhancing lesion per the treating physician, and would provide consent to undergo surgery after treatment with RT and M3814