Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma
Overview
- Phase
- Phase 3
- Intervention
- Biospecimen Collection
- Conditions
- Not specified
- Sponsor
- NRG Oncology
- Enrollment
- 163
- Locations
- 421
- Primary Endpoint
- Progression free survival (PFS)
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This randomized phase III trial studies how well radiation therapy works compared with observation in treating patients with newly diagnosed grade II meningioma that has been completely removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the extent of clinical benefit of the addition of adjuvant radiotherapy (RT) to gross total resection (GTR) for patients with newly diagnosed World Health Organization (WHO) grade II meningioma. SECONDARY OBJECTIVES: I. Overall survival (OS). II. Disease-specific survival (DSS). III. Toxicity (grade 3+, exclusive of expected alopecia). IV. Neurocognitive function (NCF). V. Patient reported outcomes (PRO) measurements. VI. Adherence to protocol-specific target and normal tissue parameters. VII. Concordance measurements of central versus parent-institution pathology. VIII. Assessment of pHH3 mitotic index and its correlation with progression-free survival (PFS) and OS. IX. Validation of the prognostic value of a 34-gene expression biomarker. X. Validation of the predictive value of a 34-gene expression biomarker in predicting the benefit of radiotherapy. XI. Tissue and specimen collection for future translational research. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo observation. Additionally, patients undergo magnetic resonance imaging (MRI) and blood collection throughout the study. ARM II: Patients undergo intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study. After completion of study treatment, patients are followed up at 3, 6, and 12 months, every 6 months for year 2 and 3, then yearly for 10 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PRIOR TO STEP 1 REGISTRATION:
- •The patient must have a newly diagnosed unifocal intracranial meningioma, gross totally resected, and histologically confirmed as WHO grade II based upon pathology findings at the enrolling institution. WHO grade will be assigned according to WHO 2016 criteria
- •Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor. GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings. The modified Simpson grade can be inferred from the operative report (surgeon does not need to explicitly describe the Simpson grade for the purposes of eligibility)
- •Step 1 registration must occur within 180 days of the initial surgery; this will provide sufficient time for post-operative imaging confirmation of resection extent after resolution of operative changes. Moreover, it will permit additional surgery if needed to achieve a GTR. Within this 180 day interval, a second surgery is permitted in order to achieve GTR, but even with a second surgery, Step 1 registration must occur within 180 days of the initial resection
- •GTR must be confirmed on post-operative imaging following the most recent surgery. For protocol enrollment, the assessment of GTR will be made at each site. However, submission of both pre-operative and post-operative MRIs is required for patients. If a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained. All sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration. The post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection. These same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery. Computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis
- •The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
- •NOTE: Central pathology review must occur between steps 1 and 2 of registration. Once appropriate pathology specimens are received, central pathology review will occur within 10 business days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
- •PRIOR TO STEP 2 REGISTRATION:
- •Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central pathology review prior to step 2 registration
- •Age \>= 18
Exclusion Criteria
- •Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
- •Definitive evidence of metastatic meningioma (metastasis, although rare, can occur and is exclusionary)
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix, melanoma in situ, or other non-invasive malignancies are permissible)
- •Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
- •Major medical illnesses or psychiatric impairments, which in the investigators opinion, will prevent administration or completion of the protocol therapy and/or preclude informed consent; these include, but are not restricted to:
- •Unstable angina and/or congestive heart failure requiring hospitalization at the time of step 2 registration
- •Transmural myocardial infarction within the last 6 months prior to step 2 registration
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
- •Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
- •Type II neurofibromatosis (NF2)
Arms & Interventions
Arm I (observation)
Patients undergo observation. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Biospecimen Collection
Arm I (observation)
Patients undergo observation. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Clinical Observation
Arm I (observation)
Patients undergo observation. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Laboratory Biomarker Analysis
Arm I (observation)
Patients undergo observation. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Magnetic Resonance Imaging
Arm I (observation)
Patients undergo observation. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Quality-of-Life Assessment
Arm II (radiation therapy)
Patients undergo IMRT or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Biospecimen Collection
Arm II (radiation therapy)
Patients undergo IMRT or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Intensity-Modulated Radiation Therapy
Arm II (radiation therapy)
Patients undergo IMRT or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Laboratory Biomarker Analysis
Arm II (radiation therapy)
Patients undergo IMRT or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Magnetic Resonance Imaging
Arm II (radiation therapy)
Patients undergo IMRT or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Proton Beam Radiation Therapy
Arm II (radiation therapy)
Patients undergo IMRT or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study.
Intervention: Quality-of-Life Assessment
Outcomes
Primary Outcomes
Progression free survival (PFS)
Time Frame: From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed up to 10 years
Kaplan-Meier method will be used to calculate the PFS rates for each of the two arms. Hazard ratio (HR) on the treatment effect will be calculated using the Cox proportional hazard model. A one-sided log-rank test will be used to test the difference in PFS between the two arms.
Secondary Outcomes
- PFS(From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed up to 5 years)
- OS rates(At 5 years)
- Disease-specific survival (DSS)(From randomization to disease-related death, assessed up to 10 years)
- DSS rates(At 5 years)
- Overall survival (OS)(From randomization to death due to any cause, assessed up to 10 years)
- Incidence of adverse events (exclusive of alopecia)(Up to 3 years)
- Adherence rate to protocol-specific target and normal tissue parameters(Up to 10 years)
- Concordance rate of central versus parent-institution pathology(Up to 10 years)
- Prognostic value of 34-gene expression biomarker(Up to 5 years)
- Predictive value of 34-gene expression biomarker(Up to 5 years)
- Change in neurocognitive function (NCF) assessed by MD Anderson Symptom Inventory with Brain Tumor (MDASI-BT)(Baseline up to 60 months)
- Change in patient reported outcomes (PRO) as assessed by MDASI-BT(Baseline up to 60 months)
- PFS(From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed at 3 years)
- DSS rates(At 3 years)