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


Title Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma
Therapeutic Area Meningiomas
Principal Investigator John Mignano, MD
Min Age 18 Years
Gender Both
Contact NCCCR Staff
617-636-3264
NCCCR@tuftsmedicalcenter.org
More Information https://clinicaltrials.gov/ct2/show/NCT03180268?term=NCT03180268&draw=2&rank=1

Overview

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.

Study Details

Inclusion Criteria

1. 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

2. 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

3. 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

Exclusion Criteria

1. Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma

2. Definitive evidence of metastatic meningioma

3. 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)

Study Requirements

Primary Outcome Measures  :

  1. 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 (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  :

  1. Overall Survival (OS) [ Time Frame: From randomization to death due to any cause, assessed up to 10 years ]

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.

  1. 5 Year Overall Survival (OS) [ Time Frame: At 5 years after randomization ]

Will be calculated based on the Kaplan-Meier curve.

  1. Disease-Specific Survival (DSS) [ Time Frame: From randomization to disease-related death, assessed up to 10 years ]

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).

  1. 3 Year Disease-Specific Survival (DSS) [ Time Frame: At 3 years after randomization ]

Will be calculated using the cumulative incidence function for each arm.

  1. 5 Year Disease-Specific Survival (DSS) [ Time Frame: At 5 years after randomization ]

Will be calculated using the cumulative incidence function for each arm.

  1. 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. ]

Will be calculated based on the Kaplan-Meier curve.

  1. 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. ]

Will be calculated based on the Kaplan-Meier curve.

  1. Neurocognitive Function (NCF) [ Time Frame: Baseline up to 60 months after randomization ]

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.

  1. Patient Reported Outcomes (PRO) as assessed by MDASI-BT [ Time Frame: Baseline up to 60 months after randomization ]

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.

  1. Assessment of pHH3 mitotic index [ Time Frame: Up to 10 years after randomization ]

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.

  1. 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 ]
The number of adverse events will be measured using the CTCAE, version 4