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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01342757
First received: April 26, 2011
Last updated: May 13, 2014
Last verified: June 2013

April 26, 2011
May 13, 2014
December 2010
May 2012   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Measurable Change on Magnetic Resonance Spectroscopy Imaging After Vorinostat Administration [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    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.
Association between magnetic resonance spectroscopy (MRS) imaging measurable biomarkers and response to vorinostat plus temozolomide [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01342757 on ClinicalTrials.gov Archive Site
Mean (or Median) Change in Metabolite Levels [ Time Frame: Baseline to 1 week ] [ Designated as safety issue: No ]
  • Change in metabolic levels for responders versus non-responders [ Designated as safety issue: No ]
  • Correlation of inositol and NAA levels with patient mood and depression [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Magnetic Resonance Spectroscopy Imaging in Predicting Response to Vorinostat and Temozolomide in Patients With Recurrent or Progressive Glioblastoma
Using Proton MRS to Predict Response of Vorinostat Treatment in Glioblastoma

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.

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.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
  • Adult Glioblastoma
  • Depression
  • Recurrent Adult Brain Tumor
  • Drug: vorinostat
    Given orally
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
  • Drug: temozolomide
    Given orally
    Other Names:
    • SCH 52365
    • Temodal
    • Temodar
    • TMZ
  • Procedure: magnetic resonance spectroscopic imaging
    Undergo MRI
    Other Names:
    • 1H-nuclear magnetic resonance spectroscopic imaging
    • Proton Magnetic Resonance Spectroscopic Imaging
  • Other: survey administration
    Ancillary studies
Experimental: 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.

Interventions:
  • Drug: vorinostat
  • Drug: temozolomide
  • Procedure: magnetic resonance spectroscopic imaging
  • Other: survey administration
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
May 2012
May 2012   (final data collection date for primary outcome measure)

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 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
  • Negative pregnancy test
  • Women of childbearing potential and men must agree to use adequate barrier contraception for the duration of study participation
  • Able to swallow capsules
  • No patients with pacemakers, non-titanium aneurysm clips, neurostimulators, cochlear implants, non-titanium metal in ocular structures, history of being a steel worker, or other incompatible implants
  • No 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
  • No history of any other cancer except non-melanoma skin cancer or carcinoma in-situ of the cervix, or cancer in complete remission and off all therapy for ≥ 3 years
  • No active infection or serious intercurrent medical illness
  • No disease that would obscure toxicity or dangerously alter drug metabolism
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA) or other agents used in this study
  • No prolonged corrected QT interval waves on baseline EKG
  • No other anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy) of any kind is permitted during the study period
  • At least 3 weeks since prior radiotherapy
  • Patients must have recovered from the toxic effects of prior therapy, including surgery
  • At least 28 days since any prior investigational agent or prior cytotoxic therapy
  • At least 23 days since prior temozolomide
  • At least 14 days since prior vincristine (42 days for nitrosourea)
  • At least 21 days since prior procarbazine
  • At least 7 days since prior non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.)
  • At least 2 weeks since prior valproic acid (or another histone deacetylase inhibitor)
  • No other concurrent investigational agents

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01342757
NCI-2011-02569, EMORY IRB #00044064, WCI-44064, R21CA141836
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Jeffrey Olson Emory University
National Cancer Institute (NCI)
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP