A Randomized Phase 3 Clinical Trial of Postoperative Radiotherapy Versus Postoperative Surveillance for Clinical Low-Risk, Molecular High-Risk Meningioma and Longitudinal Surveillance for Clinical and Molecular Low-Risk Meningioma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- NRG Oncology
- 入组人数
- 464
- 主要终点
- Progression free survival (Cohort A)
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
- •Not pregnant and not nursing
- •* Negative urine or serum pregnancy test (in persons of childbearing potential) 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 postmenopausal
- •No prior high dose radiotherapy within the last 10 years to the region of the study tumor that would result in overlap of radiotherapy fields will be allowed. High dose radiotherapy is defined as an EQD2 of 45Gy or higher, as calculated with an alpha/beta ratio of
- •Patients with known or suspected radiation-induced meningioma are eligible
- •New York Heart Association Functional Classification II or better (New York Heart Association [NYHA] Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
- •No active infection currently requiring intravenous (IV) antibiotic management
- •No known history of meningioma predisposition syndrome, such as neurofibromatosis type 2 (testing is not required)
排除标准
- 未提供
研究组 & 干预措施
Arm 1 Postoperative Surveillance
Patients undergo surveillance on study. Patients also undergo MRI throughout the trial and undergo collection of plasma, serum, and blood samples on study.
干预措施: Patient Observation (Other)
Arm 1 Postoperative Surveillance
Patients undergo surveillance on study. Patients also undergo MRI throughout the trial and undergo collection of plasma, serum, and blood samples on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm 1 Postoperative Surveillance
Patients undergo surveillance on study. Patients also undergo MRI throughout the trial and undergo collection of plasma, serum, and blood samples on study.
干预措施: Biospecimen Collection (Procedure)
Arm II Postoperative Radiotherapy
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.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm II Postoperative Radiotherapy
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.
干预措施: Biospecimen Collection (Procedure)
Arm II Postoperative Radiotherapy
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.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Arm II Postoperative Radiotherapy
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.
干预措施: Intensity-Modulated Proton Therapy (Procedure)
Arm II Postoperative Radiotherapy
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.
干预措施: Fractionated Stereotactic Radiation Therapy (Radiation)
Arm II Postoperative Radiotherapy
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.
干预措施: Neurocognitive Assessment (Other)
Arm II Postoperative Radiotherapy
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.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Progression free survival (Cohort A)
时间窗: From randomization until the first documented disease progression or death, assessed up to 5 years
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.
Progression free survival (Cohort B)
时间窗: From randomization until the first documented disease progression or death, assessed up to 5 years
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.
次要结局
- 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)
- Patient-reported neurological symptom burden (Cohort A)(Every 12 months for 5 years)
- Neurocognitive function (Cohort A)(Every 12 months for 5 years)