GlioblastomaNCT03922984
Non-Contrast Perfusion Using Arterial Spin Labeled MR Imaging for Assessment of Therapy Response in Glioblastoma
A study testing MRI with Arterial Spin Labeling (ASL) in people with Glioblastoma, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- MRI with Arterial Spin Labeling (ASL)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2019to 22 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 with histologically proven GBM
- Newly diagnosed GBM. Prior surgery is allowed, but should not have started any other treatment such as chemotherapy, radiation treatment, and anti-angiogenic therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Women of child-bearing potential must agree to undergo a urine pregnancy screening per standard Radiology departmental protocol, in place to prevent imaging of pregnant patients. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: 1) Has not undergone a hysterectomy or bilateral oophorectomy; or 2) Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Scheduled to undergo chemoradiation.
Who cannot join
- Subjects who have had prior chemotherapy or radiotherapy.
- Subjects may not be receiving any other investigational agents at the time of enrollment.
- Subjects must not be pregnant since pregnancy is a contraindication to administration of gadolinium-based contrast agents.
- Any contraindication to MRI per Radiology Department's routine protocol, e.g. MRI-incompatible objects, including but not limited to medical devices (e.g. pacemakers, automated implantable cardioverter defibrillators, etc.) and other foreign bodies.
- Known severe allergic reaction to Gadolinium-based contrast agents.
- Patients with sickle cell disease and patients with other hemolytic anemias (low red blood count in body).
- Patients with uncontrollable claustrophobia, severe lower back pain, and uncontrollable tremors, to the point that it would render them unable to tolerate an MRI study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Study to Evaluate Quantitative Non-Contrast Perfusion Using Arterial Spin Labeled Magnetic Resonance (MR) Imaging for Assessment of Therapy Response in Glioblastoma
MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first.
Clinically, GBM patients are imaged every 8-weeks, beginning at 10 weeks after the completion of chemoradiation, since morphological (i.e. size) changes are not anticipated earlier. However, our preliminary experience and others have shown functional changes including perfusion and diffusion as early as 3-weeks after the initiation of the treatment . Thus, our T10, T18, T26 and T34 MRI sessions will be performed along with the clinical imaging sessions, while the T3 and T6 MRI sessions will be performed additionally for this proposal. All MR imaging sessions will be scheduled within ±1 or ±2 weeks of the target time period, as indicated in the table.
MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. The research MR imaging may take approximately an additional 15 minutes per each imaging session. However, the T3, and T6 MR imaging sessions will be performed additionally for the purpose of this study, with each taking approximately one hour. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first.
Read the detailed description
Glioblastoma (GBM) represents about 15% of all primary brain tumors with approximately 19,000 new cases diagnosed annually. The one-, five- and ten-year survival rates for patients with GBM is 37.2%, 5.1% and 2.6% from diagnosis respectively, making it one of the most lethal cancers known, among all cancers. GBMs can be challenging to treat and new cancer therapies are continuously being developed for GBM treatment.
The high cost and potential risks associated with human trials for these experimental therapies have emphasized the need for sensitive monitoring of tumor response. Imaging approaches can play an important role in the evaluation and selection of potential new therapies with non-invasive longitudinal monitoring of treatment response. Currently, the radiological assessment of treatment outcomes predominantly relies on morphological (i.e. size) changes using the Response Evaluation Criteria in Solid Tumors (RECIST) and other similar scores. This is a major limiting factor as the effects of many therapeutic agents at the microscopic level precede the eventual changes in tumor size. One such tumor property that has gained increased attention is angiogenesis, which has been shown to support tumor proliferation and infiltration. Increasing numbers of clinical trials have begun targeting tumor vascular supplies either directly inhibiting angiogenesis (e.g. antiangiogenic therapy) or indirectly disrupting cell proliferation and eventually angiogenesis (e.g. cytotoxic chemoradiation). Such clinical trials and the eventual clinical use of these therapies would be greatly assisted by the availability of robust imaging indicators of angiogenesis (i.e. tissue perfusion).
Positron Emission Tomography (PET) using 15O-labeled water (15O-PET) is considered the gold standard for non-invasive measurement of tissue perfusion. However, the use of 15O-PET requires a cyclotron in close proximity to PET to produce short lived 15O-water (half life 2.4 min), limiting its applicability in clinical settings. Alternative imaging techniques include ultrasound using microbubbles, perfusion computed tomography (CT) using iodinated contrast agent and perfusion MRI using gadolinium based contrast agents. All of these techniques require exogenous agents, restricting their use in longitudinal monitoring of treatment response.
Arterial spin labeled (ASL) MRI has recently emerged as a quantitative imaging (QI) method to measure perfusion (or capillary blood flow) without the administration of exogenous contrast agents. ASL magnetically "labels" the highly permeable water in the blood as a tracer and measures their accumulation in the tissue of interest, without injecting any exogenous contrast. Various versions of ASL have been validated in animals using microspheres, and in humans using 15O-PET in the brain. ASL also has a number of advantages compared to dynamic contrast enhanced (DCE) and dynamic susceptibility contrast (DSC) based MR perfusion measurements. Specifically, ASL does not require exogenous agent alleviating the concerns of gadolinium accumulation or nephrogenic systemic fibrosis (NSF) in patients with impaired renal function and, unlike DCE/DSC, the contribution of vascular permeability to ASL measured perfusion is negligible enabling absolute perfusion quantification in physiological units (ml/100g/min).
- Conditions
- Glioblastoma
- Being tested
- MRI with Arterial Spin Labeling (ASL)
- Keywords
- magnetic resonance imaging, arterial spin labeling
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI with Arterial Spin Labeling (ASL)Procedure or surgery
Week 0 (Before initiation of chemoradiation): MRI with ASL will be performed along with patient's standard of care imaging session Week 3: contrast-enhanced research MRI with ASL Week 6: contrast-enhanced research MRI with ASL Week 10: MRI with ASL will be performed along with patient's standard of care imaging session Week 18: MRI with ASL will be performed along with patient's standard of care imaging session Week 26: MRI with ASL will be performed along with patient's standard of care imaging session Week 34: MRI with ASL will be performed along with patient's standard of care imaging session
| Study group | Role | What they receive |
|---|---|---|
| Glioblastoma Patients | Experimental | Patients with histologically proven glioblastoma will undergo enhanced MRI with arterial spin labeling at weeks 0, 3, 6, 10, 18, 26, and 34 after beginning standard of care treatment. Receives: Procedure: MRI with Arterial Spin Labeling (ASL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in perfusion within enhancing tumor
Will determine changes in ASL measured tumor perfusion is associated with treatment response, measured as time to progression. One-sample correlation test will be used to determine the correlation between change in ASL measured tumor perfusion (baseline to 3 weeks) and time to progression. The correlations will be measured and compared using Pearson's correlation coefficient along with 95% confidence interval.
Measured: Baseline to 3 weeks
Progression Free Survival (PFS)
Will determine if changes in ASL measured perfusion is associated with PFS. PFS will be correlated with baseline perfusion and post-treatment changes at 3-, 6- and 10-weeks compared to baseline using univariable and multivariable Cox regression models. Will determine whether changes in ASL measured tumor perfusion as a continuous variable within enhancing tumor from baseline to 3-, 6-, and 10-weeks after initiation of chemoradiation is associated with PFS. The hazard ratio and its 95% confidence interval will be presented.
Measured: Up to 3 years
Secondary outcomes (2)
ASL measured perfusion within enhancing tumor
Will determine if ASL measured tumor perfusion at baseline is associated with treatment response, measured as time to progression. One-sample correlation test will be used to determine the correlation between baseline ASL measured tumor perfusion and time to progression. The correlations will be measured and compared using Pearson's correlation coefficient along with 95% confidence interval.
Measured: Baseline
Overall Survival (OS)
Will determine if changes in ASL measured perfusion is associated with OS. OS will be correlated with baseline perfusion and post-treatment changes at 3-, 6- and 10-weeks compared to baseline using univariable and multivariable Cox regression models. Will determine whether changes in ASL measured tumor perfusion as a continuous variable within enhancing tumor from baseline to 3-, 6-, and 10-weeks after initiation of chemoradiation is associated with OS. The hazard ratio and its 95% confidence interval will be presented.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2019
- Study start16 Apr 2019
- Primary completion22 Jan 2024
- Study completion22 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Ananth Madhuranthakam, University of Texas Southwestern Medical Center
- Investigators
- Ananth Madhuranthakam, PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03922984
- Sponsor's protocol ID
- STU 032018-079
- Other IDs
- 1U01CA207091-01A1
- Status last verified
- Oct 2024
- First submitted
- 17 Apr 2019
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study to Evaluate Quantitative Non-Contrast Perfusion Using Arterial Spin Labeled Magnetic Resonance (MR) Imaging for Assessment of Therapy Response in Glioblastoma
- ClinicalTrials.gov ID
- NCT03922984
- Acronym / sponsor ID
- STU 032018-079
- Conditions
- Glioblastoma
- Keywords
- magnetic resonance imaging, arterial spin labeling
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 Apr 2019 (actual)
- Primary completion
- 22 Jan 2024 (actual)
- Study completion
- 22 Jan 2024 (actual)
- First posted
- 22 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first.
Clinically, GBM patients are imaged every 8-weeks, beginning at 10 weeks after the completion of chemoradiation, since morphological (i.e. size) changes are not anticipated earlier. However, our preliminary experience and others have shown functional changes including perfusion and diffusion as early as 3-weeks after the initiation of the treatment . Thus, our T10, T18, T26 and T34 MRI sessions will be performed along with the clinical imaging sessions, while the T3 and T6 MRI sessions will be performed additionally for this proposal. All MR imaging sessions will be scheduled within ±1 or ±2 weeks of the target time period, as indicated in the table.
MRI including ASL will be performed before, during and after the treatment, in a total of 7 MRI sessions until 8 months after the first session. The research MR imaging may take approximately an additional 15 minutes per each imaging session. However, the T3, and T6 MR imaging sessions will be performed additionally for the purpose of this study, with each taking approximately one hour. Thereafter, patients will be followed through standard clinical examinations for the next 3 years or until demise, whichever occurs first.
Detailed description
Glioblastoma (GBM) represents about 15% of all primary brain tumors with approximately 19,000 new cases diagnosed annually. The one-, five- and ten-year survival rates for patients with GBM is 37.2%, 5.1% and 2.6% from diagnosis respectively, making it one of the most lethal cancers known, among all cancers. GBMs can be challenging to treat and new cancer therapies are continuously being developed for GBM treatment.
The high cost and potential risks associated with human trials for these experimental therapies have emphasized the need for sensitive monitoring of tumor response. Imaging approaches can play an important role in the evaluation and selection of potential new therapies with non-invasive longitudinal monitoring of treatment response. Currently, the radiological assessment of treatment outcomes predominantly relies on morphological (i.e. size) changes using the Response Evaluation Criteria in Solid Tumors (RECIST) and other similar scores. This is a major limiting factor as the effects of many therapeutic agents at the microscopic level precede the eventual changes in tumor size. One such tumor property that has gained increased attention is angiogenesis, which has been shown to support tumor proliferation and infiltration. Increasing numbers of clinical trials have begun targeting tumor vascular supplies either directly inhibiting angiogenesis (e.g. antiangiogenic therapy) or indirectly disrupting cell proliferation and eventually angiogenesis (e.g. cytotoxic chemoradiation). Such clinical trials and the eventual clinical use of these therapies would be greatly assisted by the availability of robust imaging indicators of angiogenesis (i.e. tissue perfusion).
Positron Emission Tomography (PET) using 15O-labeled water (15O-PET) is considered the gold standard for non-invasive measurement of tissue perfusion. However, the use of 15O-PET requires a cyclotron in close proximity to PET to produce short lived 15O-water (half life 2.4 min), limiting its applicability in clinical settings. Alternative imaging techniques include ultrasound using microbubbles, perfusion computed tomography (CT) using iodinated contrast agent and perfusion MRI using gadolinium based contrast agents. All of these techniques require exogenous agents, restricting their use in longitudinal monitoring of treatment response.
Arterial spin labeled (ASL) MRI has recently emerged as a quantitative imaging (QI) method to measure perfusion (or capillary blood flow) without the administration of exogenous contrast agents. ASL magnetically "labels" the highly permeable water in the blood as a tracer and measures their accumulation in the tissue of interest, without injecting any exogenous contrast. Various versions of ASL have been validated in animals using microspheres, and in humans using 15O-PET in the brain. ASL also has a number of advantages compared to dynamic contrast enhanced (DCE) and dynamic susceptibility contrast (DSC) based MR perfusion measurements. Specifically, ASL does not require exogenous agent alleviating the concerns of gadolinium accumulation or nephrogenic systemic fibrosis (NSF) in patients with impaired renal function and, unlike DCE/DSC, the contribution of vascular permeability to ASL measured perfusion is negligible enabling absolute perfusion quantification in physiological units (ml/100g/min).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Glioblastoma Patients | Experimental | Procedure: MRI with Arterial Spin Labeling (ASL)Patients with histologically proven glioblastoma will undergo enhanced MRI with arterial spin labeling at weeks 0, 3, 6, 10, 18, 26, and 34 after beginning standard of care treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with histologically proven GBM
- Newly diagnosed GBM. Prior surgery is allowed, but should not have started any other treatment such as chemotherapy, radiation treatment, and anti-angiogenic therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Women of child-bearing potential must agree to undergo a urine pregnancy screening per standard Radiology departmental protocol, in place to prevent imaging of pregnant patients. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: 1) Has not undergone a hysterectomy or bilateral oophorectomy; or 2) Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Scheduled to undergo chemoradiation.
Key exclusion criteria (7 listed)
- Subjects who have had prior chemotherapy or radiotherapy.
- Subjects may not be receiving any other investigational agents at the time of enrollment.
- Subjects must not be pregnant since pregnancy is a contraindication to administration of gadolinium-based contrast agents.
- Any contraindication to MRI per Radiology Department's routine protocol, e.g. MRI-incompatible objects, including but not limited to medical devices (e.g. pacemakers, automated implantable cardioverter defibrillators, etc.) and other foreign bodies.
- Known severe allergic reaction to Gadolinium-based contrast agents.
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 |
|---|---|---|
| MRI with Arterial Spin Labeling (ASL)Week 0 (Before initiation of chemoradiation): MRI with ASL will be performed along with patient's standard of care imaging session Week 3: contrast-enhanced research MRI with ASL Week 6: contrast-enhanced research MRI with ASL Week 10: MRI with ASL will be performed along with patient's standard of care imaging session Week 18: MRI with ASL will be performed along with patient's standard of care imaging session Week 26: MRI with ASL will be performed along with patient's standard of care imaging session Week 34: MRI with ASL will be performed along with patient's standard of care imaging session | Procedure or surgery | Glioblastoma Patients |
Primary outcome
Change in perfusion within enhancing tumor
Time frame: Baseline to 3 weeks
Will determine changes in ASL measured tumor perfusion is associated with treatment response, measured as time to progression. One-sample correlation test will be used to determine the correlation between change in ASL measured tumor perfusion (baseline to 3 weeks) and time to progression. The correlations will be measured and compared using Pearson's correlation coefficient along with 95% confidence interval.
Progression Free Survival (PFS)
Time frame: Up to 3 years
Will determine if changes in ASL measured perfusion is associated with PFS. PFS will be correlated with baseline perfusion and post-treatment changes at 3-, 6- and 10-weeks compared to baseline using univariable and multivariable Cox regression models. Will determine whether changes in ASL measured tumor perfusion as a continuous variable within enhancing tumor from baseline to 3-, 6-, and 10-weeks after initiation of chemoradiation is associated with PFS. The hazard ratio and its 95% confidence interval will be presented.
2 secondary outcomes
ASL measured perfusion within enhancing tumor
Time frame: Baseline
Overall Survival (OS)
Time frame: Up to 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
- Individual participant dataSharing planned: No
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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.
Ananth Madhuranthakam, PhD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MRI with Arterial Spin Labeling (ASL) in people with Glioblastoma, run by University of Texas Southwestern Medical Center 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 5 inclusion and 7 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 22 Oct 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in perfusion within enhancing tumor (time frame: Baseline to 3 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Oct 2024.