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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Using Proton Magnetic Resonance Spectroscopy (MRS) to Predict Response of Vorinostat Treatment in Glioblastoma

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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the strength of the association between magnetic resonance spectroscopy (MRS) imaging measurable biomarkers and response to vorinostat plus temozolomide.

SECONDARY OBJECTIVES:

I. To evaluate MRS-detected inositol and N-acetylaspartate (NAA) levels (at 3 tesla) as indicators of mood alterations as measured by a self-report depression survey (IDS-SR).

OUTLINE:

Patients receive vorinostat orally (PO) once daily (QD) on days -7 to -1 (course 1 only) and days 8-14 and 22-28 and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients previously treated with standard radiotherapy and temozolomide receive maintenance temozolomide PO on days 1-5.

Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicities. Patients undergo magnetic resonance spectroscopy imaging at baseline and at approximately 1 and 8 weeks on treatment. Patients also undergo an Inventory of Depression Symptomatology Self-Reported (IDS-SR) assessment at baseline and periodically during study.

Current Primary Outcome:

• Proportion of Patients With Magnetic Resonance Spectroscopy Response to Initial Vorinostat by MRI and MRS Scans as Determined by Spectroscopic Index [ Time Frame: 9 weeks ]
  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.
• Proportion of Patients Who Experience Metabolic Restoration Between the Responders and Non-responder Groups by MRS Scans [ Time Frame: After 1 week ]
• Measurable Change on Magnetic Resonance Spectroscopy Imaging After Vorinostat Administration [ Time Frame: 9 weeks ]
  Changes in magnetic resonance spectroscopic imaging signal and semiquantitative analysis of inositol, choline, lactate, and 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.

Original Primary Outcome: Association between magnetic resonance spectroscopy (MRS) imaging measurable biomarkers and response to vorinostat plus temozolomide

Current Secondary Outcome: Mean (or Median) Change in Metabolite Levels [ Time Frame: Baseline to 1 week ]

Original Secondary Outcome:

• Change in metabolic levels for responders versus non-responders
• Correlation of inositol and NAA levels with patient mood and depression

Dates:
Date Received: April 26, 2011
Date Started: December 2010
Date Completion:
Last Updated: April 14, 2015
Last Verified: June 2014