MRSI to Predict Response to RT/TMZ ± Belinostat in GBM

NCT02137759 | Unknown Phase 2 DMC

• 6 other identifiers: IRB00065425Winship2434-13U01CA172027F30CA206291R21NS100244P30CA138292
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

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.

Conditions

Glioblastoma Multiforme of Brain

Keywords

Glioblastoma

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  9 months

Secondary Outcomes (3)

• Overall Survival

  18 months

• Progression Free Survival

  9 months

• IDS-SR score change

  11 weeks

Other Outcomes (2)

• QOL changes

  up to 2 years

• Neurocognitive function changes

  up to 2 years

Study Arms (2)

Std RT/TMZ (Cohort 1)

ACTIVE COMPARATOR

* Standard radiation therapy * Standard temozolomide

Radiation: Standard Radiation Therapy; Drug: Standard Temozolomide

Std RT/TMZ + belinostat (Cohorts 2a, 2b)

EXPERIMENTAL

* Standard radiation therapy * Standard temozolomide * Belinostat

Radiation: Standard Radiation Therapy; Drug: Standard Temozolomide; Drug: Belinostat

Interventions

Standard Radiation Therapy RADIATION

Radiation therapy to 60 Gy

Std RT/TMZ (Cohort 1); Std RT/TMZ + belinostat (Cohorts 2a, 2b)

Standard Temozolomide DRUG

Temozolomide given orally

Also known as: Temodar

Std RT/TMZ (Cohort 1); Std RT/TMZ + belinostat (Cohorts 2a, 2b)

Belinostat DRUG

Belinostat dose to be determined, given intravenously over 30-45 minutes

Also known as: Beleodaq, PXD101

Std RT/TMZ + belinostat (Cohorts 2a, 2b)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• bilirubin ≤ 2 x UNL
• creatinine ≤ 1.5 mg/dL
• Life expectancy of ≥ 12 weeks
• Karnofsky Performance Score ≥ 60
• Women of childbearing potential must have a negative beta-human chorionic gonadotropin pregnancy test documented ≤ 7 days prior to registration

You may not qualify if:

• 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)
• Has prolonged corrected QT (QTc) interval (\> 450 msec) (for cohorts 2a and 2b \[belinostat cohorts\] only, ECG not required for cohort 1)
• Taking any of the following Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes ≤ 7 days prior to registration (for cohorts 2a and 2b \[belinostat cohorts\] only)
• Quinidine, procainamide, disopyramide
• Amiodarone, sotalol, ibutilide, dofetilide
• Erythromycin, clarithromycin

Sponsors & Collaborators

• Emory University: lead
• Johns Hopkins University: collaborator
• Spectrum Pharmaceuticals, Inc: collaborator
• National Cancer Institute (NCI): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (2)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; belinostat

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Hui-Kuo Shu, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 9, 2014
• First Posted: May 14, 2014
• Study Start: May 7, 2014
• Primary Completion: August 15, 2023
• Study Completion: August 15, 2024
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)