In the first phase of this study (Cohort 1), the investigators will determine the feasibility of adding MRSI to the evaluation of newly-diagnosed GBM patients treated with standard RT/TMZ and determine whether magnetic resonance spectroscopic imaging (MRSI) can predict for better outcomes in these patients. In the second phase of this study (Cohorts 2a and 2b), the investigators will find the maximum tolerated dose of belinostat for treating newly-diagnosed GBM patients with standard RT/TMZ and will determine whether MRSI can aid clinicians in the early determination of response to this new therapy.
Patients will be assigned to Cohort 1 (standard RT/TMZ) followed by entry to either Cohort 1 or Cohort 2a (standard RT/TMZ + dose finding for belinostat), followed by assignment to Cohort 2b (standard RT/TMZ + tolerable dose of belinostat). Patients will undergo MRSI scans before beginning treatment and then at several time points during treatment to look for the early response of their tumor to treatment. Blood and tumor samples will be used to measure the levels of certain markers within the cancer cells. Patients will also be assessed for the side effects they experience. Progression-free and overall survival outcomes will be recorded. Patients will also have assessment of their depressive symptoms, quality-of-life and neurocognitive function at several time points during and after therapy course.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Radiation therapy to 60 Gy
Temozolomide given orally
Belinostat dose to be determined, given intravenously over 30-45 minutes
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Progression Free Survival (PFS) (Cohort 1)
The investigators will use a support vector machine approach to determine an MRSI 5-metabolite profile at week 3 in Cohort 1 that is predictive of prolonged PFS at 9 months.
Time frame: 9 months
Maximum Tolerated Dose of Belinostat (Cohort 2a)
The investigators will determine the maximum tolerated dose of belinostat (up to 1000 mg/day x 5 days q3weeks x 3) used with standard RT/temozolomide for newly diagnosed GBM patients.
Time frame: 9 weeks
Progression Free Survival (PFS) (Cohort 2b)
The investigators will determine if MRSI biomarkers at week 3 in GBM patients from Cohort 2b can distinguish belinostat responders from non-responders and predict improved PFS at 9 months.
Time frame: 9 months
Overall Survival
The investigators will determine whether changes in MRSI metabolite maps at day 8 (for Cohort 2 only), week 3 (for Cohort 1 and 2) and week 11 (for Cohort 1 and 2) predict for overall survival at 18 months.
Time frame: 18 months
Progression Free Survival
The investigators will determine whether changes in MRSI metabolite maps at day 8 (for Cohort 2 only) and week 11 (for Cohort 1 and 2) predict for PFS at 9 months.
Time frame: 9 months
IDS-SR score change
The investigators will determine whether changes in the MRSI metabolite map at week 11 predict for mood alterations as measure by the Inventory of Depressive Symptomatology-Self Report (IDS-SR), a validated instrument for depression assessment, in Cohorts 1 and 2.
Time frame: 11 weeks
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