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Clinical Trial Summary

This phase I trial investigates the side effects and best dose of nedisertib, 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. Nedisertib 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 nedisertib with radiation therapy may work better than radiation therapy alone in treating patients with glioblastoma or gliosarcoma.

Clinical Trial Description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of nedisertib (M3814) in combination with standard of care radiation dose (60 Gy, 2 Gy/fraction over 6 weeks) in patients with newly diagnosed MGMT unmethylated glioblastoma (GBM). (Stage I) II. To determine the ability of M3814 to cross the blood brain barrier and to evaluate their pharmacodynamic properties in resected tissue. (Stage II) SECONDARY AND EXPLORATORY OBJECTIVES: I. To evaluate the dose limiting toxicities (DLT). (Stage I) (Secondary Objective) II. To determine the overall response rate (ORR), median progression free survival (mPFS) and median overall survival (mOS) of M3814 in combination with radiation. (Stage I) (Secondary Objective) II. To determine the overall response rate (ORR), median progression free survival (mPFS) and median overall survival (mOS) of M3814 in combination with radiation. (Stage II) (Exploratory Objective) CORRELATIVE OBJECTIVES: I. To evaluate pharmacodynamic properties of M3814. II. To assess the alterations in tumor immune microenvironment as a result of deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK) inhibition. OUTLINE: This is a dose-escalation study of nedisertib. Patients are assigned to 1 of 2 stages. STAGE I (CONCURRENT): Patients undergo standard of care radiation therapy daily (Monday-Friday) for 30 fractions. Patients also receive nedisertib orally (PO) on each day of radiation therapy and given 1-2 hours before each treatment fraction. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. STAGE I (ADJUVANT): Patients receive temozolomide PO once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. STAGE II (CONCURRENT): Patients receive nedisertib and undergo standard of care radiation therapy as in Stage I. Within 1-14 days after the completion of radiation therapy, patients undergo surgical resection. STAGE II (ADJUVANT): Patients receive temozolomide as in Stage I. After completion of study treatment, patients are followed up every 3 months. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT04555577
Study type Interventional
Source M.D. Anderson Cancer Center
Contact Nazanin Majd, MD
Phone 713-792-2883
Status Recruiting
Phase Phase 1
Start date September 20, 2020
Completion date October 30, 2023

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