Clinical Trial: Natural History of Brain Function, Quality of Life, and Seizure Control in Patients With Brain Tumor Who Have Undergone Surgery

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Natural History of Postoperative Cognitive Function, Quality of Life, and Seizure Control in Patients With Supratentorial Low-Risk Grade II Glioma

Brief Summary: This trial studies the natural history of brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery. Learning about brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery may help doctors learn more about the disease and find better methods of treatment and on-going care.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine if there is difference in the average changes of neurocognitive function (NCF) scores from baseline to the time of radiologic tumor progression or up to 5 years (whichever occurs first), between radiologically progressed and non-progressed patients.

SECONDARY OBJECTIVES:

I. To determine if there is difference in the time to neurocognitive decline, as defined by the Reliable Change Index - Within subjects Standard Deviation (RCI-WSD), between radiologically progressed and non-progressed patients.

II. To evaluate NCF during the postoperative observational period of progression-free survival (PFS) and after radiological progression for a total time on study of 5 years.

III. To determine if the changes in cognitive functioning are an early warning biomarker for radiological progression.

IV. To explore the effect of salvage therapy on cognitive outcomes in patients who progress during the study period for up to 5 years.

V. To evaluate quality-of-life (QOL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL-30 and QOL brain module (BCN20) and health utilities as measured by the European Quality of Life-5 Dimensions (EQ-5D), for a total time on study of 5 years.

VI. To evaluate seizure control for a total time on study of 5 years. VII. To evaluate molecular correlates of QOL, NCF, seizure control, and PFS. VIII. To characterize aberrant molecular pathways in low-grade gliomas (LGGs) and test the hypothesis that activation of signaling pathways will predict worse
Sponsor: Radiation Therapy Oncology Group

Current Primary Outcome: NCF as measured by each of the 4 neurocognitive tests (DET, IDN, OCLT, GMLT) [ Time Frame: Up to 5 years ]

Each of the battery's tests will be evaluated using the 2-sample t-test with a 2-sided significance level of 0.05 to determine if there is a clinically meaningful difference in the average change of NCF score from baseline to the time of radiologic tumor progression or up to 5 years (whichever occurs first) between radiologically progressed and non-progressed patients. In order to adjust for multiple comparisons and maintain the overall type I error of 0.05, Hochberg's procedure will be applied.


Original Primary Outcome: NCF as measured by each of the 4 neurocognitive tests periodically for 5 years

Current Secondary Outcome:

  • Time to neurocognitive decline in patients who progress and who do not progress radiologically, as defined by the RCI-WSD [ Time Frame: Up to 5 years ]
    The cumulative incidence approach will be used to estimate the median time to neurocognitive impairment to account for the competing risk of death and to determine if there is a clinically meaningful difference in the time to neurocognitive decline, as defined by the RCI-WSD (reliable change index—within-subjects standard deviation), between radiologically progressed and non-progressed patients.
  • PFS [ Time Frame: The interval from registration to progression or death, whichever occurs first, assessed up to 5 years ]
    Estimated using the Kaplan-Meier method, and difference between the activation of different signaling pathways will be tested using the log rank test. Multivariate analyses with the Cox proportional hazards model for PFS will be performed to assess the activation of the signaling pathway effect adjusting for patient-specific risk factors. The covariates to be evaluated for the multivariate models are: activation of signaling pathway status, age, tumor size, and other prognostic factors.
  • Radiological progression [ Time Frame: Up to 5 years ]
    To determine if the NCF decline is an earlier warning biomarker to radiologic progression, we will use NCF change as a time-dependent covariate in a Cox proportional hazards (PH) regression model with radiological progression as the endpoint. The Cox model estimates the ratio of hazard rate of radiographic failure with and without neurocognitive decline. Anticonvulsant use, tumor size, tumor histology, and further treatment received if recurrence is discovered, which may also have impact on the radiological progression, will also be considered in this Cox PH regression analysis.
  • Effect of salvage therapy on cognitive outcomes in patients who progress [ Time Frame: Up to 5 years ]
  • QOL as measured by the EORTC QOL-30, EORTC QOL-BCN20, and EQ-5D [ Time Frame: Up to 5 years ]
    The general linear mixed-effects model will be used to evaluate the changes of QOL and health utilities over time.
  • Frequency of seizures, evaluated using patient seizure diary [ Time Frame: Up to 5 years ]
    Marginal models will be used to evaluate the change of frequencies of seizures over time for up to 5 years. Anticonvulsant use, tumor size, tumor histology, further treatment received if recurrence is discovered, and other prognostic factors will also be included in the covariates sets. The available molecular marker information will also be included as a covariate to evaluate the molecular correlates of seizure frequency.
  • Molecular correlates of QOL, NCF, seizure control, and PFS [ Time Frame: Up to 5 years ]
  • OS [ Time Frame: Up to 5 years ]
    Estimated using the Kaplan-Meier method, and difference between the activation of different signaling pathways will be tested using the log rank test. Multivariate analyses with the Cox proportional hazards model for OS will be performed to assess the activation of the signaling pathway effect adjusting for patient-specific risk factors. The covariates to be evaluated for the multivariate models are: activation of signaling pathway status, age, tumor size, and other prognostic factors.
  • Symptomatic or clinical progression [ Time Frame: Up to 5 years ]
    Symptomatic and clinical progression will be explored for the correlation with cognitive changes in addition to radiological progression.


Original Secondary Outcome:

  • Time to neurocognitive decline as defined by the RCI-WSD
  • PFS
  • Association of cognitive function and radiological progression
  • Effect of salvage therapy on cognitive outcomes in patients who progress
  • QOL as measured by the EORTC QLQ-C30, EORTC QLQ-BCN20, and EQ-5D
  • Frequency of seizures
  • Molecular correlates of QOL, NCF, seizure control, and PFS
  • Overall survival
  • Association between change in cognitive function and symptomatic progression or clinical progression


Information By: Radiation Therapy Oncology Group

Dates:
Date Received: August 13, 2011
Date Started: October 2011
Date Completion:
Last Updated: March 17, 2015
Last Verified: March 2015