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

Psychosocial Effects of Cancer and Its Treatment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01417507
• Other study ID #: RTOG 0925
• Secondary ID: NCI-2011-02982CD
• Status: Completed
• Phase: N/A
• First received: August 13, 2011
• Last updated: March 17, 2015
• Start date: October 2011
• Est. completion date: December 2014

Study information

• Verified date: March 2015
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 (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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Adult Diffuse Astrocytoma
• Adult Mixed Glioma
• Adult Oligodendroglioma
• Astrocytoma
• Cognitive/Functional Effects
• Neurotoxicity
• Neurotoxicity Syndromes
• Oligodendroglioma
• Psychosocial Effects of Cancer and Its Treatment
• Seizure
• Seizures

Intervention

Procedure:
• cognitive assessment
Undergo neurocognitive assessment
• magnetic resonance imaging
Undergo MRI

Other:
• laboratory biomarker analysis
Correlative studies
• questionnaire administration
Ancillary studies

Procedure:
• quality-of-life assessment
Ancillary studies

Locations

Country	Name	City	State
Canada	London Regional Cancer Program	London	Ontario
Canada	McGill University Department of Oncology	Montreal	Quebec
United States	Piedmont Hospital	Atlanta	Georgia
United States	Billings Clinic	Billings	Montana
United States	The Kirklin Clinic at Acton Road	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Evanston CCOP-NorthShore University HealthSystem	Evanston	Illinois
United States	Leeward Radiation Oncology Center	Ewa Beach	Hawaii
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hawaii Medical Center East	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	Norton Health Care Pavilion - Downtown	Louisville	Kentucky
United States	Norton Suburban Hospital	Louisville	Kentucky
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Providence Hospital	Mobile	Alabama
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	The Nebraska Medical Center	Omaha	Nebraska
United States	Florida Hospital	Orlando	Florida
United States	Radiation Therapy Oncology Group	Philadelphia	Pennsylvania
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	Arizona Oncology-Deer Valley Center	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Barnes West County Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Covenant Medical Center	Waterloo	Iowa
United States	Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	York Hospital	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NCF as measured by each of the 4 neurocognitive tests (DET, IDN, OCLT, GMLT)	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.	Up to 5 years	No
Secondary	Time to neurocognitive decline in patients who progress and who do not progress radiologically, as defined by the RCI-WSD	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.	Up to 5 years	No
Secondary	PFS	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.	The interval from registration to progression or death, whichever occurs first, assessed up to 5 years	No
Secondary	Radiological progression	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.	Up to 5 years	No
Secondary	Effect of salvage therapy on cognitive outcomes in patients who progress		Up to 5 years	No
Secondary	QOL as measured by the EORTC QOL-30, EORTC QOL-BCN20, and EQ-5D	The general linear mixed-effects model will be used to evaluate the changes of QOL and health utilities over time.	Up to 5 years	No
Secondary	Frequency of seizures, evaluated using patient seizure diary	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.	Up to 5 years	No
Secondary	Molecular correlates of QOL, NCF, seizure control, and PFS		Up to 5 years	No
Secondary	OS	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.	Up to 5 years	No
Secondary	Symptomatic or clinical progression	Symptomatic and clinical progression will be explored for the correlation with cognitive changes in addition to radiological progression.	Up to 5 years	No