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

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.

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