A Phase 3 interventional study of Patient Observation and Magnetic Resonance Imaging in Grade 1 Meningioma, Grade 2 Meningioma and Recurrent Grade 1 Meningioma, sponsored by NRG Oncology. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by NRG Oncology · Phase 3, Interventional, and Treatment
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.
255 studies on the registry are indexed under Meningioma; 85 are open to participants now.
This study's planned enrollment of 464 is above the median of 40 across 180 interventional studies indexed under Meningioma.
Browse Meningioma studies →NRG Oncology is the lead sponsor of 72 studies on the registry; 25 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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):
Central gene expression profiling for calculation of the gene expression risk score:
Not pregnant and not nursing
* Negative urine or serum pregnancy test (in persons of ) within 14 days prior to step 2 registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and who is not
Exclusion Criteria:
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Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Undergo surveillance
Undergo MRI
Undergo collection of plasma, serum, and blood samples
Undergo IMRT
Undergo IMPT
Undergo FSRT
Ancillary studies
Ancillary Studies
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.
Time frame: 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.
Time frame: From randomization until the first documented disease progression or death, assessed up to 5 years
Overall survival (Cohort A)
Analysis for overall survival will consist of estimation of its distribution for each study arm via the Kaplan-Meier method and a stratified log-rank test. Additional analyses may consist of estimating the treatment hazard ratio via the Cox proportional hazards model adjusting for randomization stratification factors, evaluating whether the proportional hazards assumption holds or whether any treatment effect is notably time-varying, and evaluating for potential treatment by prognostic covariate interactions.
Time frame: From randomization until death due to any cause, assessed up to 5 years
Overall survival (Cohort B)
Analysis for overall survival will consist of estimation of its distribution for each study arm via the Kaplan-Meier method and a stratified log-rank test. Additional analyses may consist of estimating the treatment hazard ratio via the Cox proportional hazards model adjusting for randomization stratification factors, evaluating whether the proportional hazards assumption holds or whether any treatment effect is notably time-varying, and evaluating for potential treatment by prognostic covariate interactions.
Time frame: From randomization until death due to any cause, assessed up to 5 years
Time to next treatment (TTNT) (Cohort A)
Time to next treatment (TTNT) (Cohort A)
Time frame: 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)
Adverse events (AEs) will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher AE will be compared between treatment arms. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level 0.05.
Time frame: At months 3, 6, and 12 for the first year then every 6 months for year 2
Incidence of adverse events (Cohort B)
AEs will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher AE will be compared between treatment arms. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level 0.05.
Time frame: At months 3, 6, and 12 for the first year then every 6 months for year 2
Patient-reported neurological symptom burden (Cohort A)
Will determine whether postoperative radiotherapy increases patient-reported neurological symptom burden compared with postoperative surveillance in patients with clinical low-risk, molecular high-risk meningiomas. Neurological symptom burden will be assessed using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) module, a patient-reported outcome measure in which symptom severity items are scored on a 0 to 10 numeric rating scale, where 0 = symptom not present and 10 = symptom as bad as imaginable. Higher scores indicate greater symptom burden (worse outcome). For the primary analysis evaluating between-arm differences in MDASI-BT scores over time, a general mixed-effects model for repeated measures will be fitted to assess changes in scores by treatment arm.
Time frame: Every 12 months for 5 years
Neurocognitive function (Cohort A)
Neurocognitive function will be assessed using the Trail Making Test (TMT), a measure of attention, processing speed, and executive function. Neurocognitive failure will be defined according to the protocol-specified criteria for deterioration from baseline on the TMT. TTNCF analyses will be performed as described above. TMT performance is typically measured as completion time in seconds; lower completion times indicate better neurocognitive performance and higher values indicate worse performance.
Time frame: Every 12 months for 5 years
Progression free survival by sex
Estimates of the primary outcome treatment effect and the corresponding 95% confidence intervals will be provided by sex.
Time frame: Up to 5 years
Progression free survival by race
Estimates of the primary outcome treatment effect and the corresponding 95% confidence intervals will be provided by race.
Time frame: Up to 5 years
Progression free survival by ethnicity
Estimates of the primary outcome treatment effect and the corresponding 95% confidence intervals will be provided by ethnicity.
Time frame: Up to 5 years
No study locations are listed for this record.
Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Data sharing details ↗ · grants.nih.gov
No publications or documents are linked to this record.
Start is estimated for Jan 2027; primary completion for Jun 2035, 101 months later.
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This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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