Clinical Trials /

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

NCT03180268

Description:

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.

Related Conditions:
  • Meningioma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery
  • Official Title: Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma

Clinical Trial IDs

  • ORG STUDY ID: NRG-BN003
  • SECONDARY ID: NCI-2016-01619
  • SECONDARY ID: NRG-BN003
  • SECONDARY ID: NRG-BN003
  • SECONDARY ID: NRG-BN003
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT03180268

Conditions

  • Grade II Meningioma
  • Intracranial Meningioma

Purpose

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 OBJECTIVES:

      I. To determine, in terms of progression-free survival (PFS), 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. Outcomes and 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. Tissue microarray construction, and assessment of pHH3 mitotic index and
      molecular correlates to OS.

      OUTLINE: Patients are randomized to 1 of 2 arms after undergoing gross total resection.

      ARM I: Patients undergo observation.

      ARM II: Patients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33
      fractions (59.4 Gy in 33 daily fractions of 1.8 Gy each).

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (Clinical Observation)OtherPatients undergo observation after gross total resection.
    Arm II (Radiation Therapy)ExperimentalPatients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions after gross total resection.

      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
      
                -  Step 1 registration must occur within 180 days of the initial surgery; 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
      
                -  For step 1 registration the operating neurosurgeon must provide the modified Simpson
                   grade
      
                -  GTR must be confirmed on post-operative imaging following the most recent surgery;
                   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; imaging subsequent to enrollment must include pre and
                   post gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR),
                   magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI
                   scan and an axial T2 fluid attenuated inversion recovery (FLAIR) sequence; to yield
                   acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR,
                   MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness
                   not exceeding 1.5 mm; 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
      
                -  If the patient is a primary English speaker, the patient must participate in the NCF
                   and patient reported outcomes part of the study; if the patient is a primary French or
                   Spanish speaker, the patient must participate in the patient reported outcomes part of
                   the study
      
                -  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 15 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
      
                -  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
      
              Exclusion Criteria:
      
                -  Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple
                   meningiomas, hemangiopericytoma
      
                -  Definitive evidence of metastatic meningioma
      
                -  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, etc) or receive gadolinium; 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
      
                -  Pregnancy and/or nursing females
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure: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.
      Safety Issue:
      Description:Kaplan-Meier method will be used to calculate the PFS rates for each of the two arms (Kaplan 1958). Hazard ratio (HR) on the treatment effect will be calculated using the Cox proportional hazard model (Cox 1972). A one-sided log-rank test will be used to test the difference in PFS between the two arms (Peto 1972).

      Secondary Outcome Measures

      Measure:Overall Survival (OS)
      Time Frame:From randomization to death due to any cause, assessed up to 10 years
      Safety Issue:
      Description:Kaplan-Meier method will be used to calculate the OS rates for each of the two arms (Kaplan 1958). Hazard ratio (HR) on the treatment effect will be calculated using the Cox proportional hazard model (Cox 1972). A one-sided log-rank test will be used to test the difference in OS between the two arms (Peto 1972). Cox proportional hazard model will be used to determine the adjusted treatment effect on OS, with patient pretreatment characteristics as covariates.
      Measure:5 Year Overall Survival (OS)
      Time Frame:At 5 years after randomization
      Safety Issue:
      Description:Will be calculated based on the Kaplan-Meier curve.
      Measure:Disease-Specific Survival (DSS)
      Time Frame:From randomization to disease-related death, assessed up to 10 years
      Safety Issue:
      Description:Will be calculated using the cumulative incidence function for each arm. The HR for the treatment effect on DSS will be calculated using Gray's method under the competing risk approach, with death due to non-disease related cause treated as the competing risk (Gray 1988). Multivariate analysis on DSS will be performed using the Fine-Gray model, with patient pretreatment characteristics as covariates (Fine 1999).
      Measure:3 Year Disease-Specific Survival (DSS)
      Time Frame:At 3 years after randomization
      Safety Issue:
      Description:Will be calculated using the cumulative incidence function for each arm.
      Measure:5 Year Disease-Specific Survival (DSS)
      Time Frame:At 5 years after randomization
      Safety Issue:
      Description:Will be calculated using the cumulative incidence function for each arm.
      Measure:3 Year Progression-Free Survival (PFS)
      Time Frame:From randomization to the first documented disease progression, or death due to any cause, whichever comes first, assessed at 3 years after randomization.
      Safety Issue:
      Description:Will be calculated based on the Kaplan-Meier curve.
      Measure:5 Year 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 5 years after randomization.
      Safety Issue:
      Description:Will be calculated based on the Kaplan-Meier curve.
      Measure:Neurocognitive Function (NCF)
      Time Frame:Baseline up to 60 months after randomization
      Safety Issue:
      Description:Longitudinal analysis will be performed to compare NCF over time between the 2 arms, using the NCF Clinical Trial Battery (CTB) composite score. Early change from baseline in CTB composite score will be evaluated and compared between the 2 arms using 2-sample t tests.
      Measure:Patient Reported Outcomes (PRO) as assessed by MDASI-BT
      Time Frame:Baseline up to 60 months after randomization
      Safety Issue:
      Description:Longitudinal analysis will be performed to compare symptom burden over time between the 2 arms, using the MDASI-BT. Early change from baseline in symptom burden will be evaluated and compared between the 2 arms using 2-sample t tests.
      Measure:Assessment of pHH3 mitotic index
      Time Frame:Up to 10 years after randomization
      Safety Issue:
      Description:The Kaplan-Meier method will be used to estimate the PFS and OS rates by pHH3 category. The HRs on the effect of pHH3 on PFS and OS, respectively will be calculated using the Cox proportional hazard model and will be tested using the log-rank test. Multivariate analyses will be conducted with patient pretreatment characteristics, such as age and Simpson resection grade, included as covariates.
      Measure:Incidence of adverse events as measured by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4 (exclusive of alopecia)
      Time Frame:Up to 3 years after randomization
      Safety Issue:
      Description:The number of adverse events will be measured using the CTCAE, version 4

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:NRG Oncology

      Last Updated

      January 5, 2018