Quantitative Magnetic Resonance Spectroscopic Imaging (MRSI) to Predict Early Response to Standard Radiation Therapy (RT)/Temozolomide (TMZ) ± Belinostat Therapy in Newly-Diagnosed Glioblastomas (GBM)
Overview
- Phase
- Phase 2
- Intervention
- Standard Radiation Therapy
- Conditions
- Glioblastoma Multiforme of Brain
- Sponsor
- Emory University
- Enrollment
- 29
- Locations
- 2
- Primary Endpoint
- Progression Free Survival (PFS) (Cohort 1)
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Hui-Kuo Shu
Principal Investigator
Emory University
Eligibility Criteria
Inclusion Criteria
- •Newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically
- •≥ 18 years of age
- •Able to have MRI scans
- •Measurable contrast-enhancing supratentorial tumor (≥ 0.2 cc (current resolution of MRSI is 0.108cc)) in a region amenable to MRSI
- •Have the following lab values ≤ 14 days prior to registration:
- •white blood cell count ≥ 3,000/μL
- •absolute neutrophil count ≥ 1,500/μL
- •platelet count of ≥ 100,000/μL
- •hemoglobin ≥ 10 gm/dL (transfusion is allowed to reach minimum level)
- •serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2.0x upper normal limit (UNL)
Exclusion Criteria
- •Pacemakers, non-titanium aneurysm clips, neurostimulators, cochlear implants, non-titanium metal in ocular structures, history of being a steel worker, or other incompatible implants which makes MRI safety an issue
- •Any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
- •History of any other invasive cancer (except non-melanoma skin cancer and excluding carcinoma in-situ), unless in complete remission and off of all therapy for that disease for ≥ 3 years, are ineligible
- •Active infection or serious intercurrent medical illness
- •Any disease that will obscure toxicity or dangerously alter drug metabolism
- •Receiving any other investigational agents
- •Received prior cytotoxic, non-cytotoxic or experimental drug therapies for brain tumor
- •History of prior cranial radiation
- •History of myocardial infarction or unstable angina ≤ 6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy, or life-threatening ventricular arrhythmias
- •Patients with congenital long QT syndrome (for cohorts 2a and 2b \[belinostat cohorts\] only, ECG not required for cohort 1)
Arms & Interventions
Std RT/TMZ (Cohort 1)
* Standard radiation therapy * Standard temozolomide
Intervention: Standard Radiation Therapy
Std RT/TMZ (Cohort 1)
* Standard radiation therapy * Standard temozolomide
Intervention: Standard Temozolomide
Std RT/TMZ + belinostat (Cohorts 2a, 2b)
* Standard radiation therapy * Standard temozolomide * Belinostat
Intervention: Standard Radiation Therapy
Std RT/TMZ + belinostat (Cohorts 2a, 2b)
* Standard radiation therapy * Standard temozolomide * Belinostat
Intervention: Standard Temozolomide
Std RT/TMZ + belinostat (Cohorts 2a, 2b)
* Standard radiation therapy * Standard temozolomide * Belinostat
Intervention: Belinostat
Outcomes
Primary Outcomes
Progression Free Survival (PFS) (Cohort 1)
Time Frame: 9 months
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.
Maximum Tolerated Dose of Belinostat (Cohort 2a)
Time Frame: 9 weeks
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.
Progression Free Survival (PFS) (Cohort 2b)
Time Frame: 9 months
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.
Secondary Outcomes
- Overall Survival(18 months)
- Progression Free Survival(9 months)
- IDS-SR score change(11 weeks)