Phase III Trial of Stereotactic Radiosurgery (SRS) versus Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for 10 or fewer Brain Metastases from Small Cell Lung Cancer (NRG-CC009)

May 10 2023

The NRG Oncology clinical trial NRG-CC009 is a phase III trial that will be comparing two procedures for patients with 10 or fewer brain metastases from their small cell lung cancer (SCLC).The trial will compare stereotactic radiosurgery (SRS), a focused high-dose radiation therapy delivered only to the areas of brain cancer that avoids the surrounding normal brain tissue, to a type of whole brain radiotherapy that avoids the hippocampus (HA-WBRT), or the memory-specific hippocampal neural stem cells in the brain, along with the drug memantine that is used to preserve cognition.

“The current standard of care for patients who develop brain metastases from their small cell lung cancer is hippocampal-avoidant whole-brain radiotherapy. However, emerging data suggest that SRS may also be appropriate. In this trial, we are seeking to determine if the use of SRS for this patient population leads to better cognitive toxicity outcomes,” stated Vinai Gondi, MD, the Director of Research at the Northwestern Medicine Proton Center, Co-Director of the Brain Tumor Center at the Northwestern Medicine Cancer Center Warrenville, and Principal Investigator of the NRG-CC009 trial.

“In the NRG-CC009 trial, if a strategy of SRS alone is associated with improved cognitive function compared to a strategy of hippocampal-avoidance WBRT plus memantine, these results could establish SRS alone as a standard option for patients with brain metastases from small-cell lung cancer.” added Chad Rusthoven, MD, of the University of Colorado and the Co-Principal Investigator of the NRG-CC009 trial.

NRG-CC009 was activated in February 2021. The trial will stratify trial participants by their disease-specific graded prognostic assessment results and their prior exposure to neurocognitive function testing by participation on the ongoing SWOG S1827 (MAVERICK) study (a randomized trial of brain MRI surveillance +/- prophylactic cranial irradiation (PCI) in small-cell lung cancer patients without brain metastases). Then, patients will be randomly assigned to receive either SRS or to receive HA-WBRT plus the drug memantine taken for up to 6 months.

The primary goal of the trial is to determine which treatment is better at preventing cognitive function failure or cognitive decline via a standard battery of cognitive tests, including the Hopkins Verbal Learning Test (Revised), Controlled Oral Word Association test, and the Trail Making Test. Important secondary endpoints will include overall survival, neurologic mortality, intracranial disease control, salvage procedures, patient-reported outcomes, and symptom burden. Correlative endpoints will include cost-effectiveness, brain MRI imaging biomarkers, and specimen banking for future translational research.

Learn more about this trial at

Protocol documents and materials are located on the CTSU website.

NRG-CC009 has a patient-facing study webpage available as well on the NRG website at

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