Adult GlioblastomaNCT01342757
Magnetic Resonance Spectroscopy Imaging in Predicting Response to Vorinostat and Temozolomide in Patients With Recurrent or Progressive Glioblastoma
A study testing vorinostat, temozolomide and magnetic resonance spectroscopic imaging in people with Adult Glioblastoma and Depression, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Glioblastoma, Depression, Recurrent Adult Brain Tumor
- What is being tested?
- vorinostat, temozolomide and magnetic resonance spectroscopic imaging
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to May 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 35Show fewer
- 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
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Using Proton Magnetic Resonance Spectroscopy (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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the strength of the association between magnetic resonance spectroscopy (MRS) imaging measurable biomarkers and response to vorinostat plus temozolomide.
SECONDARY OBJECTIVES:
- 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.
- Conditions
- Adult Glioblastoma, Depression, Recurrent Adult Brain Tumor
- Being tested
- vorinostat, temozolomide, magnetic resonance spectroscopic imaging, survey administration
- Medical subject headings
- Glioblastoma, Depression, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vorinostatDrug
Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Given orally
temozolomideDrug
Also called SCH 52365, Temodal, Temodar, TMZ
Given orally
magnetic resonance spectroscopic imagingProcedure or surgery
Also called 1H-nuclear magnetic resonance spectroscopic imaging, Proton Magnetic Resonance Spectroscopic Imaging
Undergo MRI
survey administrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: vorinostat; Drug: temozolomide; Procedure: magnetic resonance spectroscopic imaging; Other: survey administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)).
Measured: 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.
Measured: 9 weeks
Secondary outcomes (1)
Mean Change in Metabolite Levels
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. The change of metabolite level in choline (Cho) and N-acetyl aspartate (NAA) were calculated in ratio by (metabolite after treatment / metabolite before treatment - 1). The reported ratios represent the Cho-to-NAA ratio at day 7 compared with day 0.
Measured: Baseline to 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2011 (estimated)
- Study startDec 2010
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jeffrey Olson, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01342757
- Sponsor's protocol ID
- NCI-2011-02569
- Other IDs
- EMORY IRB #00044064, WCI-44064, R21CA141836
- Status last verified
- Jan 2018
- First submitted
- 26 Apr 2011
- Last updated
- 29 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 25055291
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Proton Magnetic Resonance Spectroscopy (MRS) to Predict Response of Vorinostat Treatment in Glioblastoma
- ClinicalTrials.gov ID
- NCT01342757
- Acronym / sponsor ID
- NCI-2011-02569
- Conditions
- Adult Glioblastoma, Depression, Recurrent Adult Brain Tumor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2010
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 27 Apr 2011 (estimated)
- Results
- Posted 11 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To evaluate the strength of the association between magnetic resonance spectroscopy (MRS) imaging measurable biomarkers and response to vorinostat plus temozolomide.
SECONDARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: vorinostat, Drug: temozolomide, Procedure: magnetic resonance spectroscopic imaging, Other: survey administrationPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Patients must have 1 of the following:
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vorinostatAlso: L-001079038, SAHA, suberoylanilide hydroxamic acid, ZolinzaGiven orally | Drug | Arm I |
| temozolomideAlso: SCH 52365, Temodal, Temodar, TMZGiven orally | Drug | Arm I |
| magnetic resonance spectroscopic imagingAlso: 1H-nuclear magnetic resonance spectroscopic imaging, Proton Magnetic Resonance Spectroscopic ImagingUndergo MRI | Procedure or surgery | Arm I |
| survey administrationAncillary studies | Other | Arm I |
Primary outcome
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)).
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.
1 secondary outcome
Mean Change in Metabolite Levels
Time frame: Baseline to 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25055291Shim 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Olson principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing vorinostat, temozolomide and magnetic resonance spectroscopic imaging in people with Adult Glioblastoma and Depression, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01342757, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2018.