Magnetic Resonance Spectroscopy Imaging in Predicting Response to Vorinostat and Temozolomide in Patients With Recurrent or Progressive Glioblastoma

NCT01342757 | Completed Results DMC

• 4 other identifiers: NCI-2011-02569EMORY IRB #00044064WCI-44064R21CA141836
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is studying magnetic resonance spectroscopy imaging in predicting response in patients to vorinostat and temozolomide in patients with recurrent, progressive, or newly diagnosed glioblastoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help temozolomide work better by making tumor cells more sensitive to the drug. Imaging procedures, such as magnetic resonance spectroscopy imaging, may help measure the patient's response to vorinostat and temozolomide and allow doctors to plan better treatment.

Conditions

Adult Glioblastoma; Depression; Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (3)

• Proportion of Patients With Magnetic Resonance Spectroscopy (MRS) Response to Initial Vorinostat by MRI and MRS Scans as Determined by Spectroscopic Index

  Changes in magnetic resonance spectroscopic imaging signal and semiquantitative analysis of inositol, choline, lactate, and N-acetylaspartate signal are measured. The values for each of these metabolites are normalized to baseline at one and nine weeks. The values of all the metabolites at one week are added and this is the magnetic resonance spectroscopic index for one week. This is done again at nine weeks. The number is unitless and there is no range limit. Positive values represent normalization of tumor metabolism and negative values suggest no improvement or worsening of metabolic character.

  9 weeks

• Proportion of Patients Who Experience Metabolic Restoration Between the Responders and Non-responder Groups by MRS Scans

  Baseline MRS was performed 1-3 days before initiation of treatment. Follow-up MRS studies were performed at day 7. A standard quadrature head coil was used to collect MR data. A responder was defined as stable disease: determined in glioblastoma to be between a 25% volume increase and 50% volume decrease compared to baseline imaging at the therapy initiation at the 2 month follow-up visit. The spectroscopic restoration index was calculated (ΔN-acetyl aspartate + Δcreatine + Δmyo-inositol - Δcholine - Δ(lactate / lipids)).

  After 1 week

• Measurable Change on Magnetic Resonance Spectroscopy Imaging After Vorinostat Administration

  Changes in magnetic resonance spectroscopic imaging signal and semiquantitative analysis of inositol, choline, lactate, and N-acetyl aspartate (NAA) signal are measured. The values for each of these metabolites are normalized to baseline at one and nine weeks. The values of all the metabolites at one week are added and this is the magnetic resonance spectroscopic index for one week. This is done again at nine weeks. The number is unitless and there is no range limit. Positive values represent normalization of tumor metabolism and negative values suggest no improvement or worsening of metabolic character.

  9 weeks

Secondary Outcomes (1)

• Mean Change in Metabolite Levels

  Baseline to 1 week

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive vorinostat once daily on days -7 to -1 (course 1 only) and days 8-14 and 22-28 and temozolomide on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance spectroscopic imaging at baseline and at approximately 1 and 8 weeks on treatment. Patients also undergo a survey administration of Inventory of Depression Symptomatology Self-Reported (IDS-SR) assessment at baseline and periodically during study.

Drug: vorinostat; Drug: temozolomide; Procedure: magnetic resonance spectroscopic imaging; Other: survey administration

Interventions

vorinostat DRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I

temozolomide DRUG

Given orally

Also known as: SCH 52365, Temodal, Temodar, TMZ

Arm I

magnetic resonance spectroscopic imaging PROCEDURE

Undergo MRI

Also known as: 1H-nuclear magnetic resonance spectroscopic imaging, Proton Magnetic Resonance Spectroscopic Imaging

Arm I

survey administration OTHER

Ancillary studies

Arm I

Eligibility Criteria

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

You may qualify if:

• Patients must have 1 of the following:
• Diagnosis of recurrent or progressive glioblastoma
• Patients with recurrent disease may have had treatment for any number of prior relapses
• Newly diagnosed glioblastoma and have completed radiation therapy and are receiving standard follow-up temozolomide
• Must be able to have an MRI, and have a measurable contrast-enhancing supratentorial tumor of at least 1 cm by shortest diameter
• Residual disease following resection measuring 1 cm in diameter or greater is mandated for eligibility into the study
• Patients must have a stable or progressive disease as determined by serial brain MRI using the McDonald Criteria on a scan 14 days or fewer before registration and on a stable steroid dose for 5 days
• Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or thallium scanning, MR spectroscopy, or surgical documentation of disease
• White Blood Cell Count \> 3,000/μL
• Absolute Neutrophil Count \> 1,500/μL
• Platelet count \> 100,000/μL
• Hemoglobin \> 10 g/dL (transfusion allowed)
• Serum glutamate oxaloacetate transaminase \< 2 times upper limit of normal (ULN)
• Bilirubin \< 2 times ULN
• Creatinine \< 1.5 mg/dL

You may not qualify if:

• Diagnostic and Statistical Manual-IV Axis I or II diagnosis (as determined by PI), exclusive of nicotine dependence.
• Pregnant.
• Contraindications to MRI: pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants.
• Active medical or neurological disorder.
• History of alcohol or drug dependence

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Shim H, Wei L, Holder CA, Guo Y, Hu XP, Miller AH, Olson JJ. Use of high-resolution volumetric MR spectroscopic imaging in assessing treatment response of glioblastoma to an HDAC inhibitor. AJR Am J Roentgenol. 2014 Aug;203(2):W158-65. doi: 10.2214/AJR.14.12518.

  PMID: 25055291 RESULT

MeSH Terms

Conditions

Glioblastoma; Depression; Brain Neoplasms

Interventions

Vorinostat; Temozolomide; Magnetic Resonance Spectroscopy

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; Behavioral Symptoms; Behavior; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Limitations and Caveats

In five of the twelve cases spectroscopic indices could not be calculated because the tumor volume was outside of reliably measured voxels. These were primarily accounted for by tumor closeness to the skull or the small size of residual tumor.

Results Point of Contact

• Title: Jeffrey J. Olson, MD
• Organization: Emory University School of Medicine

jolson@emory.edu

404-778-3091

Study Officials

• Jeffrey Olson

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: April 27, 2011
• Study Start: December 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: January 29, 2018
• Results First Posted: June 11, 2014

Record last verified: 2018-01

Locations

US (1)