NRG Oncology NCORP Research Base-BIQSFP

July 8, 2025 Brandy Heckman Stoddard, PhD, MPH, Division of Cancer Prevention National Cancer Institute 9609 Medical Center Drive East Building, 5th Floor MSC-9786 Rockville, MD 20850 RE: NRG Oncology Network Group Operations Center – Application for NRG-CC017 (formerly NRG-CC2403) Quality of Life BIQSFP Dear Dr. Heckman-Stoddard: Attached is our application and budget to support a Quality of Life BIQSFP for NRG-CC017 (formerly NRG-CC2403). The parent concept, NRG-CC2403, was approved by the DCP on March 5th and the protocol subsequently designated NRG-CC017. The NRG-CC017 protocol was submitted to the DCP on June 6, 2025. • Project Title: Real Time Integral Neurocognitive Function (NCF) Testing in NRG-CC017 • Parent Protocol: A randomized phase III study comparing temporally-modulated pulsed radiation therapy (TMPRT) versus standard radiation therapy with temozolomide for older adults with newly diagnosed MGMT-unmethylated glioblastoma (NRG-CC017) • Principal Investigator: Jeffrey Wefel, PhD • Description: NRG-CC017 is a proposed phase III randomized trial comparing standard delivery radiation therapy (RT) to temporally-modulated pulsed RT (TMPRT) in the treatment of older (≥65 y) patients with newly diagnosed, MGMT promoter unmethylated glioblastoma (GBM). TMPRT is hypothesized to have lower risk of neurotoxicity. The primary endpoint of the phase III is time to NCF failure as measured by the Clinical Trial Battery (CTB). This BIQSFP application proposes to conduct serial, longitudinal neurocognitive function (NCF) testing using the CTB as a real-time integral study outcome. The CTB is composed of the Hopkins Verbal Learning Test – Revised (HVLT-R), Trail Making Test (TMT), and Controlled Oral Word Association (COWA). Due to the limitations of small single-arm phase II studies, it is essential to validate the potential of TMPRT to prolong OS while maintaining NCF in a more robust randomized setting. Considering the prior preclinical and single-arm phase II data, we anticipate that TMPRT will not only improve tumor control but will also reduce normal tissue injury underlying NCF decline. As a real time integral study outcome, patients will complete NCF testing using the CTB at registration, one month after RT (month 2), and every 2 months thereafter until month 12 at the same time points that imaging studies of the brain and clinical staging evaluations are performed as per standard clinical care. This allows us to evaluate the differential impact of treatment effects versus progressive disease in the brain on NCF test results. Page 2 • Type of Study: Integral BIQSFP • Budget: Direct Costs: Year 1 - $247,854 Total Budget – $1,247,354 Indirect Costs: Year 1 - $5,478; Total Budget - $27,567 Total Costs: Year 1 – $253,332; Total Budget - $1,274,921 • Duration: 39 months We have attached a scientific proposal and budget for this project. If you have any questions, please contact Meg Dowds at dowdsm@NRGOncology.org or 412-339-5304. We wish to thank you for this opportunity and look forward to beginning this project. Sincerely, Deborah Watkins Bruner, RN, PhD NRG NCORP Principal Investigator cc: Wolf Lindwasser, PhD NCIBIQSFP@mail.nih.gov enc: