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

NCT07785687 | Not Yet Recruiting Phase 3

• 2 other identifiers: NRG-BN015NCI-2026-05558
• Study Type: interventional
• Target: 464
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Grade 1 Meningioma; Grade 2 Meningioma; Recurrent Grade 1 Meningioma

Outcome Measures

Primary Outcomes (2)

• Progression free survival (Cohort A)

  The log-rank test will be used to test the difference in PFS between the arms. Will estimate progression free survival by arm using the method of Kaplan-Meier. Cox proportional hazards model will be used to estimate the treatment hazard ratio and 95% confidence interval.

  From randomization until the first documented disease progression or death, assessed up to 5 years

• Progression free survival (Cohort B)

  A one-sided 5% level Wald test will be used to determine if the observed hazard for progression free survival is better than that specified under the null hypothesis. Will estimate progression free survival using the method of Kaplan-Meier. Greenwood's formula will be used to estimate the confidence intervals for 5-year progression free survival.

  From randomization until the first documented disease progression or death, assessed up to 5 years

Secondary Outcomes (7)

• Overall survival (Cohort A)

  From randomization until death due to any cause, assessed up to 5 years

• Overall survival (Cohort B)

  From randomization until death due to any cause, assessed up to 5 years

• Time to next treatment (TTNT) (Cohort A)

  From randomization until reoperation in the prior surgical bed or prior radiotherapy field, re-irradiation in the prior surgical bed or radiotherapy field, or initiation of systemic meningioma-directed medical therapy, assessed up to 5 years

• Incidence of adverse events (Cohort A)

  At months 3, 6, and 12 for the first year then every 6 months for year 2

• Incidence of adverse events (Cohort B)

  At months 3, 6, and 12 for the first year then every 6 months for year 2

Other Outcomes (3)

• Progression free survival by sex

  Up to 5 years

• Progression free survival by race

  Up to 5 years

• Progression free survival by ethnicity

  Up to 5 years

Study Arms (2)

Arm 1 Postoperative Surveillance

EXPERIMENTAL

Patients undergo surveillance on study. Patients also undergo MRI throughout the trial and undergo collection of plasma, serum, and blood samples on study.

Other: Patient Observation; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection

Arm II Postoperative Radiotherapy

EXPERIMENTAL

Patients undergo IMRT or IMPT 5 days per week for a total of 30 fractions over 50 days or undergo 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.

Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Intensity-Modulated Proton Therapy; Radiation: Fractionated Stereotactic Radiation Therapy; Other: Neurocognitive Assessment; Other: Questionnaire Administration

Interventions

Patient Observation OTHER

Undergo surveillance

Arm 1 Postoperative Surveillance

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Arm 1 Postoperative Surveillance; Arm II Postoperative Radiotherapy

Biospecimen Collection PROCEDURE

Undergo collection of plasma, serum, and blood samples

Arm 1 Postoperative Surveillance; Arm II Postoperative Radiotherapy

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Arm II Postoperative Radiotherapy

Intensity-Modulated Proton Therapy PROCEDURE

Undergo IMPT

Arm II Postoperative Radiotherapy

Fractionated Stereotactic Radiation Therapy RADIATION

Undergo FSRT

Arm II Postoperative Radiotherapy

Neurocognitive Assessment OTHER

Ancillary studies

Arm II Postoperative Radiotherapy

Questionnaire Administration OTHER

Ancillary Studies

Arm II Postoperative Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Radiologically confirmed newly diagnosed or recurrent solitary (n=1) cranial World Health Organization (WHO) grade 1 meningioma post GTR or STR based on postoperative MRI findings, or newly diagnosed solitary WHO grade 2 meningioma post GTR based on postoperative MRI findings at the enrolling institution. Somatostatin receptor (SSTR)-directed positron emission tomography (PET) imaging may not be used to define extent of resection or meningioma number
• Histologically confirmed as WHO grade 1 or 2, based on pathology findings at the enrolling institution according to WHO 2021 criteria
• Initial surgery (GTR or STR) within 180 days prior to step 1 registration (within this 180-day period, a second surgery is permitted to achieve GTR):
• GTR is defined as the absence of gross residual meningioma, as confirmed by postoperative MRI
• STR is defined as the presence of gross residual meningioma, as confirmed by postoperative MRI
• Surgeon-reported Simpson grade of resection, meningioma location, and any available SSTR-directed PET imaging studies will be assembled
• Postoperative MRI prior to step 1 registration. It is additionally required that all imaging sequences obtained in all preoperative and postoperative MRI, and any computed tomography (CT) or SSTR-direct PET imaging studies used for radiotherapy planning be submitted to NRG Oncology after step 1 registration. SSTR PET imaging may be used for radiotherapy planning to ensure all disease is encompassed in the clinical target volume (CTV) but may not be used to shrink the CTV or to supersede MRI-defined extent of resection or meningioma number
• NOTE: Central review for pathology, radiology, and gene expression profiling must occur between step 1 and step 2 of registration. Once appropriate pathology and imaging data are received, central pathology and radiology review will occur within 10 business days and must confirm WHO grade 1 meningioma after GTR or STR or WHO grade 2 meningioma after GTR. Gene expression profiling will occur within 30 business days of receiving appropriate pathology specimens. Central review for pathology, radiology, and gene expression must be completed before the patient can proceed to step 2 registration/randomization. For patients with central confirmation of clinical low-risk, molecular high-risk meningioma who will be eligible for cohort A randomization, central determination of 54 gray (Gy)/30 fractions (Fx) or 25Gy/5Fx radiotherapy and recommended radiotherapy treatment volumes will be provided prior to step 2 registration. See the study-specific biospecimen collection and submission manual on the Cancer Trials Support Unit (CTSU) protocol website for details of central pathology review and gene expression biomarker testing
• Age ≥ 18
• Central radiology confirmation of solitary (n=1) cranial meningioma on preoperative MRI and extent of resection (GTR or STR) on postoperative MRI
• Central histological pathology confirmation of newly diagnosed or recurrent WHO grade 1 meningioma after GTR or STR, or newly diagnosed WHO grade 2 meningioma after GTR, according to WHO 2021 criteria
• Central gene expression profiling for calculation of the gene expression risk score:
• Cohort A: High gene expression risk score after GTR or STR, or intermediate gene expression risk score after STR
• Cohort B: Low gene expression risk score after GTR or STR, or intermediate gene expression risk score after GTR
• Postoperative Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Sponsors & Collaborators

• NRG Oncology: lead

MeSH Terms

Interventions

Watchful Waiting; Magnetic Resonance Spectroscopy; Radiotherapy, Intensity-Modulated; Mental Status and Dementia Tests

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2026
• First Posted: August 25, 2026
• Study Start (Estimated): January 28, 2027
• Primary Completion (Estimated): June 30, 2035
• Study Completion (Estimated): June 30, 2040
• Last Updated: August 25, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share