GliosarcomaNCT03843814
Pilot Study Using Amide Proton Transfer Magnetic Resonance Imaging Distinguishing Glioma
A study testing APT MRI in people with Gliosarcoma and Glioma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
This research is being done to study the pattern of changes in various parts of the magnetic resonance imaging (MRI) studies that patients have done to help plan their radiation therapy and to evaluate the effects of therapy. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Gliosarcoma, Glioma
- What is being tested?
- APT MRI
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to 13 Dec 2017
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically Confirmed Glioma after completion of planned biopsy or resection.
- High grade glioma histologies:
- Glioblastoma
- High Grade or Malignant Glioma
- Anaplastic Astrocytoma
- Anaplastic Oligodendroglioma
Show all 15Show fewer
- Gliosarcoma
- Mixture of any of the above histologies Low Grade Histologies
- Astrocytoma
- Grade II or low grade glioma
- Oligodendroglioma
- Mixtures of the above histologies
- Plan to undergo external radiation treatment as part of therapy
- No prior therapeutic cranial radiotherapy
- Can safely perform clinically indicated MRI (no contraindications to MRI with Gadolinium) as determined by the standard Johns Hopkins Radiation Oncology screening procedures,
Who cannot join
- Patients who cannot undergo MRIs.
- Patients who are allergic to gadolinium based contrast agent
- Patients who have cardiac pacemaker or other electronic or metal implant
- Patients who have chronic kidney disease judged sufficient to exclude them from the clinically indicated contrast enhanced MRI.
- Female patients who is pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
The SKCCC at Johns Hopkins
Baltimore, Maryland, 21287
About this study
Official title: A Pilot Study Using Amide Proton Transfer (APT) Magnetic Resonance Imaging to Distinguish Tumor Bearing Cancerous Tissue From Normal Tissue in Patients With Glioma.
This research is being done to study the pattern of changes in various parts of the magnetic resonance imaging (MRI) studies that patients have done to help plan their radiation therapy and to evaluate the effects of therapy.
The MRI of the brain is one of the major ways a participant's doctors determine how to treat a participant's tumor and if the participant's tumor is growing or not. In this study the investigators want to learn if new sequences added to the MRI that the investigators are already getting to guide partipants' radiation treatment can be analyzed to help make better treatment decisions. MRI sequences that examine the composition and structure of the tissues in the brain in a different way will be obtained. These are called called Amide Proton Transfer (APT) and Diffusion Weighted MRI.
Read more
These scans will first be performed at the time of participants' radiation plannings scan done before treatment and near the end of the course of radiation treatments. This will allow the study team to investigate if there are changes in these sequences before radiation treatment and to see if using these MRI studies will allow us to better plan radiation treatments for patients in the future. This pre-treatment scan will be done at the same time as participants' standard radiation planning MRI, but will cause the scan to take longer. Participants will also have an extra MRI during one of the last 5 days of the planned 28-33 radiation treatments that are standardly used. This additional scan will not include administration of injected contrast agents, and would occur on a day when participants are also coming in for radiation. This scan will be compared with the first scan. The investigators will determine whether these changes may predict later long term outcome of treatment for patients. Patients who enroll in this study will get all of the standard therapy they would get for their tumor whether or not they participate in this study. There is no extra or different therapy given.
The investigators anticipate that the radiation treatment volumes created using APT will largely overlap with the conventional plan but will be distinct at the margins. Disease failure is more likely to occur in areas with APT abnormalities suggestive of active tumor. In patients that have failure outside the contrast enhancing area, the region of failure will be predicted by regions of increased APT activity. Current MRI sequences do not allow for prediction of regions of recurrence or progression, or distinguish between tumor, pressure, or surgical injury as the cause of FLAIR/T2 abnormalities. Disease failure is more likely to occur in areas with APT abnormalities suggestive of active tumor. In patients that have failure outside the contrast enhancing area, the region of failure will be predicted by regions of increased APT activity. Current MRI sequences do not allow for prediction of regions of recurrence or progression, or distinguish between tumor, pressure, or surgical injury as the cause of FLAIR/T2 abnormalities. Volume containing elevated APT signal may be associated with outcome (survival). In an exploratory analysis, the investigators will evaluate whether there are characteristic patterns that should be prospectively studied in a larger trial.
Read the detailed description
Currently, all brain tumors are routinely evaluated using gadolinium contrast-enhanced (Gd-CE) MRI, in combination with T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI, which are used to determine the extent of tumor involvement to guide treatments, and to assess therapeutic response. However, Gd-CE only depicts disruption of the blood brain barrier and is not specific for tumor activity. Therefore, standard MRI may not be optimal in defining the true extent of tumor, defining as abnormal areas that may contain only edema related to mass effect or surgery and miss tumor extensions that do not sufficiently disrupt the blood-brain-barrier. In addition, in the setting of radiation therapy which also disrupts the blood brain barrier, it does not serve as an early marker of tumor response.
The primary goal of the current observational study is to explore whether Amide Proton Transfer (APT) imaging can better determine the extent of tumor involvement. APT signal is created by mobile cytoplasmic proteins, which are increased in malignant brain tumors and have been found in preclinical and clinical studies to be associated with a high APT weighted signal in glioma. Such imaging may provide information that may improve the ability of MR imaging to guide targeting of radiotherapy. In particular, it may (1) detect tumor bearing brain that is not contrast enhancing on the standard brain MRI scan for patients with high grade glioma and/or (2) fail to confirm tumor in areas of brain identified as abnormal on standard MRI. The investigators will also explore patterns of disease failure in patients with malignant gliomas to validate the observations, and whether such imaging may predict outcome.
Similar questions may be important in the therapy of low grade glioma, and an exploratory informational cohort of patients with this less common diagnosis will be accrued during the study period to inform decisions about whether further study is desirable.
A second APT image will be obtained during the final week of treatment for enrolled patients to determine whether changes in APT signal occur, and whether there is evidence that this may be prognostic for treatment success or failure when correlated with progression free survival and survival outcome. Currently, there is no imaging method to assess tumor response and predict outcome within the first several months as a result of the confounding effect of radiation on both the tumor and surrounding brain. In addition, standard brief apparent diffusion coefficient (ADC) MRI sequences will be performed as part of the pretreatment imaging and the end of treatment scan as an additional potential early imaging biomarker that may be a part of multiparametric assessment of response to radiotherapy as identified in preclinical studies performed at Johns Hopkins.
These first steps may form the basis for possible future studies to assess new approaches to radiation planning for patients with brain cancer.
- Conditions
- Gliosarcoma, Glioma
- Being tested
- APT MRI
- Keywords
- MRI (Magnetic Resonance Imaging) of the brain, Amide Proton Transfer (APT), Diffuse Weighted Imaging (DWI)
- Medical subject headings
- Gliosarcoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APT MRIProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| APT MRI | Experimental | Participants will have the standard MRI of the brain that is performed for radiation planning for brain tumors.
1. Addition of the additional MRI sequences to the standard MRI before radiation therapy. This typically adds 10-15 minutes to the length of the scan.
2. An additional MRI scan to be scheduled during one of the final five radiation treatment days that would not otherwise occur. There will be no contrast injection as part of this second scan. This may typically take 40-45 minutes.
3. Collection of information about participants' tumor, including copies of their MRIs and later outcome of treatment. Receives: Procedure: APT MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Standard planning versus Amide Proton Transfer (APT) imaging planning
Difference in radiation target volumes between standard MRI and Amide Proton Transfer (APT) imaging.
Measured: day 23-28 post radiation treatment
Secondary outcomes (4)
tumor recurrence
Number of days from Day 23-28 (end of radiation) to tumor recurrence
Measured: up to 3 years
Survival
Number of months from end of radiation therapy until death
Measured: up to 3 years
Time to absolute change in voxels of APT and DWI (diffusion weighted imaging) signals from baseline to end of radiation treatment
Number of days to absolute change in voxels at the end of radiation treatment.
Measured: Change from Baseline to Days 23-28 post-radiation treatment
Change in voxels of APT and DWI signals
Change in voxels of APT and DWI signal or pattern during the course of radiation treatment assessed at 3 years or until death, whichever occurs first.
Measured: up to 3 years or until death, whichever occurs first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2019
- Study startAug 2014
- Primary completion13 Dec 2017
- Study completion13 Dec 2017
Why it stopped: Imaging results were not sufficient or of good quality; therefore, we will not move further with the project.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliosarcomaStudies of the same condition, open and under way.
- 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lawrence Kleinberg, M.D., Principal investigator, The SKCCC at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03843814
- Sponsor's protocol ID
- J1439
- Other IDs
- IRB00032866
- Status last verified
- Nov 2019
- First submitted
- 18 Sep 2014
- Last updated
- 26 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Using Amide Proton Transfer (APT) Magnetic Resonance Imaging to Distinguish Tumor Bearing Cancerous Tissue From Normal Tissue in Patients With Glioma.
- ClinicalTrials.gov ID
- NCT03843814
- Acronym / sponsor ID
- J1439
- Conditions
- Gliosarcoma, Glioma
- Keywords
- MRI (Magnetic Resonance Imaging) of the brain, Amide Proton Transfer (APT), Diffuse Weighted Imaging (DWI)
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Imaging results were not sufficient or of good quality; therefore, we will not move further with the project.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- 13 Dec 2017 (actual)
- Study completion
- 13 Dec 2017 (actual)
- First posted
- 18 Feb 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.
This research is being done to study the pattern of changes in various parts of the magnetic resonance imaging (MRI) studies that patients have done to help plan their radiation therapy and to evaluate the effects of therapy.
The MRI of the brain is one of the major ways a participant's doctors determine how to treat a participant's tumor and if the participant's tumor is growing or not. In this study the investigators want to learn if new sequences added to the MRI that the investigators are already getting to guide partipants' radiation treatment can be analyzed to help make better treatment decisions. MRI sequences that examine the composition and structure of the tissues in the brain in a different way will be obtained. These are called called Amide Proton Transfer (APT) and Diffusion Weighted MRI.
These scans will first be performed at the time of participants' radiation plannings scan done before treatment and near the end of the course of radiation treatments. This will allow the study team to investigate if there are changes in these sequences before radiation treatment and to see if using these MRI studies will allow us to better plan radiation treatments for patients in the future. This pre-treatment scan will be done at the same time as participants' standard radiation planning MRI, but will cause the scan to take longer. Participants will also have an extra MRI during one of the last 5 days of the planned 28-33 radiation treatments that are standardly used. This additional scan will not include administration of injected contrast agents, and would occur on a day when participants are also coming in for radiation. This scan will be compared with the first scan. The investigators will determine whether these changes may predict later long term outcome of treatment for patients. Patients who enroll in this study will get all of the standard therapy they would get for their tumor whether or not they participate in this study. There is no extra or different therapy given.
The investigators anticipate that the radiation treatment volumes created using APT will largely overlap with the conventional plan but will be distinct at the margins. Disease failure is more likely to occur in areas with APT abnormalities suggestive of active tumor. In patients that have failure outside the contrast enhancing area, the region of failure will be predicted by regions of increased APT activity. Current MRI sequences do not allow for prediction of regions of recurrence or progression, or distinguish between tumor, pressure, or surgical injury as the cause of FLAIR/T2 abnormalities. Disease failure is more likely to occur in areas with APT abnormalities suggestive of active tumor. In patients that have failure outside the contrast enhancing area, the region of failure will be predicted by regions of increased APT activity. Current MRI sequences do not allow for prediction of regions of recurrence or progression, or distinguish between tumor, pressure, or surgical injury as the cause of FLAIR/T2 abnormalities. Volume containing elevated APT signal may be associated with outcome (survival). In an exploratory analysis, the investigators will evaluate whether there are characteristic patterns that should be prospectively studied in a larger trial.
Detailed description
Currently, all brain tumors are routinely evaluated using gadolinium contrast-enhanced (Gd-CE) MRI, in combination with T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI, which are used to determine the extent of tumor involvement to guide treatments, and to assess therapeutic response. However, Gd-CE only depicts disruption of the blood brain barrier and is not specific for tumor activity. Therefore, standard MRI may not be optimal in defining the true extent of tumor, defining as abnormal areas that may contain only edema related to mass effect or surgery and miss tumor extensions that do not sufficiently disrupt the blood-brain-barrier. In addition, in the setting of radiation therapy which also disrupts the blood brain barrier, it does not serve as an early marker of tumor response.
The primary goal of the current observational study is to explore whether Amide Proton Transfer (APT) imaging can better determine the extent of tumor involvement. APT signal is created by mobile cytoplasmic proteins, which are increased in malignant brain tumors and have been found in preclinical and clinical studies to be associated with a high APT weighted signal in glioma. Such imaging may provide information that may improve the ability of MR imaging to guide targeting of radiotherapy. In particular, it may (1) detect tumor bearing brain that is not contrast enhancing on the standard brain MRI scan for patients with high grade glioma and/or (2) fail to confirm tumor in areas of brain identified as abnormal on standard MRI. The investigators will also explore patterns of disease failure in patients with malignant gliomas to validate the observations, and whether such imaging may predict outcome.
Similar questions may be important in the therapy of low grade glioma, and an exploratory informational cohort of patients with this less common diagnosis will be accrued during the study period to inform decisions about whether further study is desirable.
A second APT image will be obtained during the final week of treatment for enrolled patients to determine whether changes in APT signal occur, and whether there is evidence that this may be prognostic for treatment success or failure when correlated with progression free survival and survival outcome. Currently, there is no imaging method to assess tumor response and predict outcome within the first several months as a result of the confounding effect of radiation on both the tumor and surrounding brain. In addition, standard brief apparent diffusion coefficient (ADC) MRI sequences will be performed as part of the pretreatment imaging and the end of treatment scan as an additional potential early imaging biomarker that may be a part of multiparametric assessment of response to radiotherapy as identified in preclinical studies performed at Johns Hopkins.
These first steps may form the basis for possible future studies to assess new approaches to radiation planning for patients with brain cancer.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| APT MRI | Experimental | Procedure: APT MRIParticipants will have the standard MRI of the brain that is performed for radiation planning for brain tumors. 1. Addition of the additional MRI sequences to the standard MRI before radiation therapy. This typically adds 10-15 minutes to the length of the scan. 2. An additional MRI scan to be scheduled during one of the final five radiation treatment days that would not otherwise occur. There will be no contrast injection as part of this second scan. This may typically take 40-45 minutes. 3. Collection of information about participants' tumor, including copies of their MRIs and later outcome of treatment. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Pathologically Confirmed Glioma after completion of planned biopsy or resection.
- Plan to undergo external radiation treatment as part of therapy
- No prior therapeutic cranial radiotherapy
- Can safely perform clinically indicated MRI (no contraindications to MRI with Gadolinium) as determined by the standard Johns Hopkins Radiation Oncology screening procedures,
Key exclusion criteria (5 listed)
- Patients who cannot undergo MRIs.
- Patients who are allergic to gadolinium based contrast agent
- Patients who have cardiac pacemaker or other electronic or metal implant
- Patients who have chronic kidney disease judged sufficient to exclude them from the clinically indicated contrast enhanced MRI.
- Female patients who is pregnant
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 |
|---|---|---|
| APT MRI | Procedure or surgery | APT MRI |
Primary outcome
Standard planning versus Amide Proton Transfer (APT) imaging planning
Time frame: day 23-28 post radiation treatment
Difference in radiation target volumes between standard MRI and Amide Proton Transfer (APT) imaging.
4 secondary outcomes
tumor recurrence
Time frame: up to 3 years
Survival
Time frame: up to 3 years
Time to absolute change in voxels of APT and DWI (diffusion weighted imaging) signals from baseline to end of radiation treatment
Time frame: Change from Baseline to Days 23-28 post-radiation treatment
Change in voxels of APT and DWI signals
Time frame: up to 3 years or until death, whichever occurs first.
Results and safety
The study was stopped early (reason given: Imaging results were not sufficient or of good quality; therefore, we will not move further with the project.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2019.
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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.
Lawrence Kleinberg, M.D. principal investigator
The SKCCC at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing APT MRI in people with Gliosarcoma and Glioma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 15 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: stopped early, as of the sponsor's last update on 26 Nov 2019. 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 was stopped early (reason given: Imaging results were not sufficient or of good quality; therefore, we will not move further with the project.). Results are not available in the source record.
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?
Standard planning versus Amide Proton Transfer (APT) imaging planning (time frame: day 23-28 post radiation treatment). 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 26 Nov 2019.