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)
• Be willing and able to provide written informed consent for the trial. Participants with cognitive impairment will be enrolled. Cognitive function will be assessed by the treating physician or designee through a neurological examination. The formal consent for such participants will be obtained from their legally authorized representative. For cognitively impaired adults who are enrolling in the study by consent of a legally authorized representative, assent of the subject is required for the subjects with the ability to communicate assent. This assent will be documented in subject fs consent note.
• Age 18 years or older
• Histologically confirmed World Health Organization (WHO) grade 4 glioma (GBM) or gliosarcoma, IDH wild-type, per WHO 2021 classification .IDH status is to be determined by IDH1 R132H immunohistochemistry except for patients ≤ age 54 in whom IDH sequencing will be required to detect non-canonical IDH mutations.
• Have KPS of 3 60 or ECOG . 2 according to appendix 5.
• A baseline MRI of brain obtained no more than 14 days prior to study enrollment on a stable or tapering dose of steroids for at least 3 days
• Demonstrate adequate organ function as defined below.
• All screening labs should be performed within 14 days prior to Day 1 of the study.
• 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.
• All screening labs should be performed within 14 days prior to Day 1 of the study.
• 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.
• 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.
⁃ Newly diagnosed GBM only
• 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 cancer treatments following surgery Recurrent GBM only
• Any number of recurrences
• Presence of enhancing, resectable disease
• Candidate for re-radiation with ability to meet optic nerve and brainstem departmental dose constraints per treating physicians
• 6 mos or more since last radiation
• Has not received re-radiation for GBM in the past except for stereotactic radiosurgery