Comparing Radiation After Surgery to Observation After Surgery in Patients With Clinical Low-Risk, Molecular High-Risk Meningioma, and Evaluating Observation After Surgery in Patients With Clinical and Molecular Low-Risk Meningioma

Overview

This phase III trial compares post-surgical surveillance to post-surgical radiation therapy for improving survival without disease progression in clinically low-risk patients with a grade 1 meningioma that is new or that has come back after a period of improvement (recurrent) or a new grade 2 meningioma who have undergone surgery. Post-surgical surveillance involves closely watching a patient's condition but not giving treatment unless there are changes in test results. Active surveillance avoids problems that may be caused by treatments such as radiation or surgery. It is used to find early signs that the condition is getting worse. During active surveillance, patients will be given certain exams and tests done on a regular schedule. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. The usual approach for low grade and low clinical risk meningiomas is surgery followed by radiation or no further treatment (observation) based on clinical risk factors such as tumor grade and the amount of tumor able to be removed. Clinical factors such as meningioma grade and the amount of meningioma that was removed help doctors decide whether radiation or observation is better after surgery. In this study, a patient's molecular risk, as determined using biomarkers, is also considered when assigning treatment. For patients with grade 1 or 2 meningiomas with a low clinical risk but high molecular risk of growing or coming back after surgery, this study will compare the usual approach of post-surgery observation to another usual approach of post-surgery radiation. Using high molecular risk to decide usual treatment and receiving the usual radiation could increase the amount of time without the tumor growing or coming back, but it could also cause side effects. For patients with grade 1 or 2 meningiomas with a low clinical risk and low molecular risk of growing or coming back after surgery, this study will evaluate if using molecular risk shows a greater benefit of the usual post-surgery observation.

PRIMARY OBJECTIVES: I. To determine if progression free survival (PFS) is improved with postoperative radiotherapy compared to postoperative surveillance for patients with clinical low-risk, molecular high-risk meningiomas, as defined using a centralized 34-gene expression biomarker and centralized neuro-radiology review. (Cohort A) II. To determine if 5-year PFS is greater than 90% with postoperative surveillance for patients with clinical and molecular low-risk meningiomas, as defined using a centralized 34-gene expression biomarker and centralized neuro-radiology review. (Cohort B) SECONDARY OBJECTIVES: I. To determine if overall survival (OS) of patients with clinical low-risk, molecular high-risk meningiomas is improved with postoperative radiotherapy compared to postoperative surveillance. (Cohort A) II. To determine if the time-to-next-treatment of patients with clinical low-risk, molecular high-risk meningiomas is improved with postoperative radiotherapy compared to postoperative surveillance. (Cohort A) III. To define the safety and tolerability of postoperative radiotherapy for patients with clinical low-risk, molecular high-risk meningiomas using Common Terminology Criteria for Adverse Events (CTCAE) 5.0. (Cohort A) IV. To determine if postoperative radiotherapy leads to increased neurocognitive function (NCF) deterioration, as assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R), the Controlled Oral Word Association Test (COWA), and the Trail Making Tests (TMT) A and B, as compared to postoperative surveillance for patients with clinical low-risk, molecular high-risk meningiomas. (Cohort A) V. To determine if postoperative radiotherapy leads to increased patient-reported neurological symptom burden, as measured by the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) module, as compared to postoperative surveillance for patients with clinical low-risk, molecular high-risk meningiomas. (Cohort A) VI. To define the OS of patients with clinical and molecular low-risk meningiomas with postoperative surveillance. (Cohort B) VII. To define the safety profile of postoperative surveillance for patients with clinical and molecular low-risk meningiomas using CTCAE 5.0. (Cohort B) EXPLORATORY OBJECTIVE: I. To explore additional biomarkers in pre-treatment tumor tissue, blood, or serum that may elucidate the efficacy, safety, or tolerability of postoperative radiotherapy compared to postoperative surveillance. OUTLINE: Patients with a high gene expression risk score after gross total resection (GTR) or subtotal resection (STR) or intermediate gene expression risk score after STR (Cohort A) are randomized to 1 of 2 arms. Patients with low gene expression risk score after GTR or STR or intermediate gene expression risk score after GTR (Cohort B) are assigned to Arm I. ARM I: Patients undergo surveillance on study. Patients also undergo magnetic resonance imaging (MRI) throughout the trial and undergo collection of plasma, serum, and blood samples on study. ARM II: Patients undergo intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) 5 days per week for a total of 30 fractions over 50 days or undergo fractionated stereotactic radiation therapy (FSRT) for a total of 5 fractions over 10 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI and collection of plasma, serum, and blood samples throughout the trial. After completion of study treatment, patients are followed up at 3, 6, and 12 months, every 6 months in years 2 and 3, and then yearly in years 4 and 5.