Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery

Официальное название

Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Biospecimen Collection
  Undergo collection of blood samples
• Другое Clinical Observation
  Undergo observation
• Лучевая терапия Intensity-Modulated Radiation Therapy
  Undergo IMRT
• Другое Laboratory Biomarker Analysis
  Correlative studies
• Процедура Magnetic Resonance Imaging
  Undergo MRI
• Лучевая терапия Proton Beam Radiation Therapy
  Undergo proton beam radiation therapy
• Другое Quality-of-Life Assessment
  Ancillary studies

Первичные конечные точки

• Progression free survival (PFS) [Срок оценки: From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed up to 10 years]

Вторичные конечные точки (12)

• PFS [Срок оценки: From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed at 3 years]
• PFS [Срок оценки: From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed up to 5 years]
• Disease-specific survival (DSS) [Срок оценки: From randomization to disease-related death, assessed up to 10 years]
• DSS rates [Срок оценки: At 3 years]
• DSS rates [Срок оценки: At 5 years]
• Overall survival (OS) [Срок оценки: From randomization to death due to any cause, assessed up to 10 years]
• OS rates [Срок оценки: At 5 years]
• Incidence of adverse events (exclusive of alopecia) [Срок оценки: Up to 3 years]
• Adherence rate to protocol-specific target and normal tissue parameters [Срок оценки: Up to 10 years]
• Concordance rate of central versus parent-institution pathology [Срок оценки: Up to 10 years]
• Prognostic value of 34-gene expression biomarker [Срок оценки: Up to 5 years]
• Predictive value of 34-gene expression biomarker [Срок оценки: Up to 5 years]

Критерии участия

Критерии включения

• 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
• History/physical examination, including neurologic examination within 60 days prior to step 2 registration
• Post-operative Zubrod performance status 0-1 within 60 days prior to step 2 registration
• If the patient is a woman is of childbearing potential, a serum pregnancy test, obtained within 14 days prior to step 2 registration, must be negative, and, if randomized to receive radiation therapy, the woman must agree to use contraception

Критерии исключения

• 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)
• Ailments entailing substantial increases in sensitivity and side effect risk from radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human immunodeficiency virus (HIV) with CD4 count < 200 cells/microliter); HIV testing is not required for eligibility for this protocol, and known HIV positive patients are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to step 2 registration
• Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction). Note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 198 центров

• University of Alabama at Birmingham Cancer Center — Birmingham
• Saint Joseph's Hospital and Medical Center — Phoenix
• Mayo Clinic Hospital in Arizona — Phoenix
• Mayo Clinic in Arizona — Scottsdale
• University of Arizona Cancer Center-Orange Grove Campus — Tucson
• Banner University Medical Center - Tucson — Tucson
• University of Arizona Cancer Center-North Campus — Tucson
• Kaiser Permanente-Anaheim — Anaheim
• … и ещё 190 центров

Канада · 8 центров

Список центров уточняется — проверьте первичный протокол.

Япония · 7 центров

Список центров уточняется — проверьте первичный протокол.

Индия · 1 центр

Список центров уточняется — проверьте первичный протокол.

Саудовская Аравия · 1 центр

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT03180268 · NRG-BN003 · NCI-2016-01619 · NRG-BN003 · NRG-BN003 · NRG-BN003 · U10CA180868

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗