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

This study is currently recruiting participants.
Verified December 2013 by Radiation Therapy Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01417507
First received: August 13, 2011
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Adult Diffuse Astrocytoma
Adult Mixed Glioma
Adult Oligodendroglioma
Cognitive/Functional Effects
Neurotoxicity
Psychosocial Effects of Cancer and Its Treatment
Seizure
Procedure: cognitive assessment
Procedure: magnetic resonance imaging
Other: laboratory biomarker analysis
Other: questionnaire administration
Procedure: quality-of-life assessment

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History of Postoperative Cognitive Function, Quality of Life, and Seizure Control in Patients With Supratentorial Low-Risk Grade II Glioma

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • NCF as measured by each of the 4 neurocognitive tests (DET, IDN, OCLT, GMLT) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • QOL as measured by the EORTC QOL-30, EORTC QOL-BCN20, and EQ-5D [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • OS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Symptomatic and clinical progression will be explored for the correlation with cognitive changes in addition to radiological progression.


Biospecimen Retention:   Samples With DNA

Tissue will be submitted to the RTOG Biospecimen Resource for the purpose of central review of pathology (mandatory fo eligibility), tissue banking, and translational research (highly recommended). For central review, H&E slide and tumor block must be submitted. For tissue banking and translational research, remaining tissue from the central review will be used and plasma, whole blood and urine will be collected.


Estimated Enrollment: 170
Study Start Date: October 2011
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Supportive care (neurocognitive assessment and MRI)

Patients undergo neurocognitive assessment using the CogState Test battery (the DET, the IDN, the OCLT, and the GMLT) at baseline* and at 12, 24, 36, 42, 48, 54, and 60 months. Patients also complete the EORTC QOL-30, the BCM20, and the EQ-5D questionnaires at baseline*, at 12, 24, 36, 48, and 60 months afterwards, and before undergoing any further treatment. Patients are instructed to complete a seizure and medication diary during study.

Patients undergo MRI scans at baseline*, at 12, 24, 36, 48, and 60 months, and at the time of radiological, clinical, or neurological failure.

Procedure: cognitive assessment
Undergo neurocognitive assessment
Procedure: magnetic resonance imaging
Undergo MRI
Other Names:
  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

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 PFS and overall survival (OS).

IX. To explore the relationship between change in cognitive function and symptomatic progression (defined as worsening seizures or new or progressive neurologic deficits) or clinical progression (defined as initiation of treatment interventions such as radiotherapy, chemotherapy, or additional surgery).

OUTLINE:

Patients undergo neurocognitive assessment using the CogState Test battery (the Detection Test (DET), the Identification Test (IDN), the One Card Learning Test (OCLT), and the Groton Maze Learning Test (GMLT)) at baseline* and at 12, 24, 36, 42, 48, 54, and 60 months. Patients also complete the EORTC Quality of Life Questionnaire-Core 30 (QOL-30), the Brain Cancer Module-20 (BCM20), and the European Quality of Life-5 Dimensions (EQ-5D) questionnaires at baseline*, at 12, 24, 36, 48, and 60 months afterwards, and before undergoing any further treatment. Patients are instructed to complete a seizure and medication diary during study.

Patients undergo MRI scans at baseline*, at 12, 24, 36, 48, and 60 months, and at the time of radiological, clinical, or neurological failure.

NOTE: * 12 weeks after surgery.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Central pathology-confirmed diagnosis of supratentorial grade II oligodendroglioma, astrocytome or mixed oligoastrocytoma prior to Step 2 registration.

The patient must be within one of the following categories:

Maximal safe resection with minimal residual disease defined as follows:

  • Removal of T2/FLAIR abnormalities thought to be primarily tumor, with a residual ≤ 2 cm maximal tumor diameter/T2 FLAIR abnormality on MRI to be done within 84 days postoperatively.
  • Patients who require a second surgery to obtain a maximal safe resection will be eligible if the second surgery is performed within 84 days of the inital diagnostic procedure.

OR Age <40 (any extent of resection) OR Age <50, preoperative tumor diameter <4 cm (any extent of resection)

Criteria

Inclusion Criteria:

  • Central pathology confirmed diagnosis of supratentorial grade II oligodendroglioma, astrocytoma, or mixed oligoastrocytoma prior to step 2 registration
  • No multifocal disease, based upon the following minimum diagnostic work-up:

    • History/physical examination, including neurologic examination, within 84 days prior to step 2 registration
    • Brain MRI with and without contrast within 84 days prior to Step 2 registration (Note: MRI 70 days after surgery is preferred and highly encouraged)
  • The patient must be within one of the following categories:

    • Maximal safe resection with minimal residual disease defined as follows:

      • Removal of T2/fluid-attenuated inversion recovery (FLAIR) abnormalities thought to be primarily tumor, with a residual ≤ 2 cm maximal tumor diameter/T2 FLAIR abnormality on MRI to be done within 84 days post-operatively
      • If there is > 2 cm post-operative residual T2/FLAIR abnormality and the neurosurgeon believes this represents edema and not primarily tumor, the neurosurgeon is encouraged to repeat imaging within the allowed study period (up to 84 days post-operatively) to confirm resolution of edema

        • MRI at the time of enrollment must document a ≤ 2 cm residual maximal tumor diameter/T2 FLAIR abnormality
      • Patients who required a second surgery to obtain a maximal safe resection will be eligible if the second surgery is performed within 84 days of the initial diagnostic procedure
    • Age < 40 (any extent of resection)
    • Age < 50 and preoperative tumor diameter < 4 cm (any extent of resection)
  • Karnofsky performance status ≥ 80%
  • No prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free for a minimum of 3 years [1,095 days] (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Must be able to undergo MRI of the brain with gadolinium
  • No plans for adjuvant radiotherapy or chemotherapy after surgery
  • No more than 84 days (12 weeks) since prior surgery
  • No brain tumor recurrence
  • No prior brain tumor surgery, radiation therapy and/or chemotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01417507

  Show 41 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Ali Choucair Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01417507     History of Changes
Other Study ID Numbers: RTOG 0925, NCI-2011-02982, CDR0000708271, U10CA037422
Study First Received: August 13, 2011
Last Updated: December 20, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Astrocytoma
Glioma
Oligodendroglioma
Seizures
Neurotoxicity Syndromes
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Poisoning
Substance-Related Disorders

ClinicalTrials.gov processed this record on April 14, 2014