Using Proton Magnetic Resonance Spectroscopy (MRS) to Predict Response of Vorinostat Treatment in Glioblastoma
Overview
- Phase
- Not Applicable
- Intervention
- vorinostat
- Conditions
- Adult Glioblastoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Measurable Change on Magnetic Resonance Spectroscopy Imaging After Vorinostat Administration
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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 Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Arm I
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.
Intervention: vorinostat
Arm I
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.
Intervention: temozolomide
Arm I
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.
Intervention: magnetic resonance spectroscopic imaging
Arm I
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.
Intervention: survey administration
Outcomes
Primary Outcomes
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 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.
Proportion of Patients With Magnetic Resonance Spectroscopy (MRS) 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
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)).
Secondary Outcomes
- Mean Change in Metabolite Levels(Baseline to 1 week)