Clinical trial NCT01417507: Natural History of Brain Function, Quality of Life, and Seizure Control in Patients With Brain Tumor Who Have Undergone Surgery
Official title: Natural History of Postoperative Cognitive Function, Quality of Life, and Seizure Control in Patients With Supratentorial Low-Risk Grade II Glioma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Adult Diffuse Astrocytoma
Adult Mixed Glioma
Adult Oligodendroglioma
Cognitive/Functional Effects
Neurotoxicity
Psychosocial Effects of Cancer and Its Treatment
Seizure
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2011-08-16
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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 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 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 (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

Primary outcomes:
measure: NCF as measured by each of the 4 neurocognitive tests (DET, IDN, OCLT, GMLT)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Time to neurocognitive decline in patients who progress and who do not progress radiologically, as defined by the RCI-WSD
timeFrame: Up to 5 years
measure: PFS
timeFrame: The interval from registration to progression or death, whichever occurs first, assessed up to 5 years
measure: Radiological progression
timeFrame: Up to 5 years
measure: Effect of salvage therapy on cognitive outcomes in patients who progress
timeFrame: Up to 5 years
measure: QOL as measured by the EORTC QOL-30, EORTC QOL-BCN20, and EQ-5D
timeFrame: Up to 5 years
measure: Frequency of seizures, evaluated using patient seizure diary
timeFrame: Up to 5 years
measure: Molecular correlates of QOL, NCF, seizure control, and PFS
timeFrame: Up to 5 years
measure: OS
timeFrame: Up to 5 years
measure: Symptomatic or clinical progression
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Kirklin Clinic at Acton Road
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: Providence Hospital
state: Alabama
city: Phoenix
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology-Deer Valley Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Ewa Beach
country: United States
facility: Leeward Radiation Oncology Center
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Medical Center East
state: Hawaii
city: Evanston
country: United States
facility: Evanston CCOP-NorthShore University HealthSystem
state: Illinois
city: Waterloo
country: United States
facility: Covenant Medical Center
state: Iowa
city: Louisville
country: United States
facility: Norton Health Care Pavilion - Downtown
state: Kentucky
city: Louisville
country: United States
facility: Norton Suburban Hospital
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Barnes West County Hospital
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Omaha
country: United States
facility: The Nebraska Medical Center
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Gettysburg
country: United States
facility: Adams Cancer Center
state: Pennsylvania
city: Hanover
country: United States
facility: Cherry Tree Cancer Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Radiation Therapy Oncology Group
state: Pennsylvania
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Mary's Hospital
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Community Memorial Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
Study officials:
affiliation: Radiation Therapy Oncology Group
name: Ali Choucair
role: PRINCIPAL_INVESTIGATOR
References: