Trial record 4 of 4 for:    vorinostat and glioma | Open Studies

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
Hui-Kuo Shu, MD, PhD, Emory University
ClinicalTrials.gov Identifier:
NCT02137759
First received: May 9, 2014
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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 (Cohort 2), the investigators will treat newly-diagnosed GBM patients with vorinostat and standard RT/TMZ and determine whether MRSI can aid clinicians in the early determination of response to this new therapy.


Condition Intervention Phase
Glioblastoma Multiforme of Brain
Radiation: Standard Radiation Therapy
Drug: Standard Temozolomide
Drug: Vorinostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Quantitative Magnetic Resonance Spectroscopic Imaging (MRSI) to Predict Early Response to Standard Radiation Therapy (RT)/Temozolomide (TMZ) ± Vorinostat Therapy in Newly-Diagnosed Glioblastoma (GBM) Patients

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Progression Free Survival (PFS) (Cohort 1) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    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.

  • PFS (Cohort 2) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    The investigators will determine if MRSI biomarkers at week 3 in GBM patients from Cohort 2 can distinguish vorinostat responders from non-responders and predict improved PFS at 9 months.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    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.

  • IDS-SR score change [ Time Frame: 11 weeks ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • QOL changes [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    The investigators will determine whether changes in MRSI metabolite maps correlate with changes in subjects' quality-of-life (QOL) as measured by the EORTC QLQ-C30 & BN20 and the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT), validated instruments for assessing QOL in brain tumor patients.

  • Neurocognitive function changes [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    The investigators will determine whether changes in MRSI metabolite maps correlate with changes in subjects' neurocognitive function as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R), the Controlled Oral Word Association (COWA) Test and the Trail Making Test (TMT) Parts A & B, validated instruments for evaluating neurocognitive function in brain tumor patients.


Estimated Enrollment: 90
Study Start Date: May 2014
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Std RT/TMZ (Cohort 1)
standard radiation therapy standard temozolomide
Radiation: Standard Radiation Therapy Drug: Standard Temozolomide
Experimental: Std RT/TMZ + vorinostat (Cohort 2)
standard radiation therapy standard temozolomide vorinostat
Radiation: Standard Radiation Therapy Drug: Standard Temozolomide Drug: Vorinostat

Detailed Description:

Patients (45 in each Cohort) will be sequentially enrolled to Cohort 1 (standard RT/TMZ for 6 wks followed by adjuvant TMZ) and then Cohort 2 (standard RT/TMZ + vorinostat for 6 weeks followed by adjuvant TMZ).

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
    • 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
  • All men and women of childbearing potential must agree to use adequate barrier contraception for the duration of study participation and for 12 weeks after the last dose of study drug (If pregnancy or suspected pregnancy occur while participating in study, treating physician should be informed immediately)
  • Understand and provide written informed consent
  • Both men and women, and members of all races and ethnic groups are eligible for this trial (Subjects will be approximately representative of the demographics of the referral base for the participating institutions)
  • Able to swallow capsules
  • Willing to provide mandatory tissue samples (unstained slides) for research purposes
  • Willing to forego other cytotoxic and non-cytotoxic therapies against the tumor while being treated on this protocol

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 cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for ≤ 3 years
  • 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
  • Has prolonged corrected QT (QTc) interval (>450 msec)
  • 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

    • Quinidine, procainamide, disopyramide
    • Amiodarone, sotalol, ibutilide, dofetilide
    • Erythromycin, clarithromycin
    • Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
    • Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
  • Taking valproic acid 2 weeks prior to initiation of vorinostat therapy
  • Residual enhancing tumor that lies completely within 1-2 cm of the inner table of the skull (Please consult study neuroradiologist or study PIs at your site if there is uncertainty regarding this exclusion criteria)
  • May not be enrolled on any other therapeutic trial for which they are receiving an anti-tumor therapy. (Note: patients on the standard therapy arm of another GBM trial that otherwise meets eligibility requirements for this trial remains eligible for Cohort 1)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02137759

Locations
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Hui-Kuo Shu, MD/PhD    888-946-7447    hgshu@emory.edu   
Sponsors and Collaborators
Emory University
Johns Hopkins University
  More Information

No publications provided

Responsible Party: Hui-Kuo Shu, MD, PhD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT02137759     History of Changes
Other Study ID Numbers: IRB00065425, Winship2434-13
Study First Received: May 9, 2014
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Emory University:
Glioblastoma

Additional relevant MeSH terms:
Glioma
Vorinostat
Glioblastoma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Histone Deacetylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014