Intracranial TumorsNCT02431572
A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy
A study testing PBR PET, Cancer Immunotherapy and Radiation and chemotherapy in people with Intracranial Tumors and Glioblastoma, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
This research study is studying the changes in primary and metastatic brain tumor inflammation using positron emission tomography (PET) imaging using a radioactive substance called [11C] PBR28a, which is also known as peripheral benzodiazepine receptors (PBR), or PBR-PET. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracranial Tumors, Glioblastoma, Melanoma
- What is being tested?
- PBR PET, Cancer Immunotherapy and Radiation and chemotherapy
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2015to Feb 2019
- 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
- Participants must have evidence of metastatic melanoma to the brain for Cohort A or histologically confirmed GBM for Cohorts Band C.
- Those with newly diagnosed GBM but suspected to have pseudoprogression after completion of chemoradiation can enroll in Cohort C.
- Participants must have measurable brain disease, defined as at least one lesion that is 10 mm in diameter.
- Age > 18 years.
- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
- Life expectancy of greater than 3 months.
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- Participants must have normal organ and marrow function as defined below:
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine within normal institutional limits
- --- OR
- creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- For Cohort A, only patients with metastatic melanoma to the brain for whom their treating physician has planned to give immunotherapy as monotherapy are eligible for this study. This can be in the setting of a clinical trial or not.
- For Cohort B, only patients with GBM for whom their treating physician has planned to give immunotherapy are eligible for this study. This can be in the setting of a clinical trial or not.
- For Cohort C, patients with newly diagnosed GBM who have completed standard temozolomide + radiation and have suspected pseudoprogression within the first 3 months of completing chemoradiation can enroll.
- Patient must be able to undergo MRI and PET scans.
- Patient must be maintained on a stable corticosteroid regimen for 5 days prior each MR-PET scan.
- High or mixed affinity binders (Ala/Ala or Ala/Thr) based on genotyping result from PBR affinity test. This blood test will be performed as part of the screening process after consent has been obtained.
- The effects of PBR on the developing human fetus are unknown. For this reason and because radiopharmaceuticals agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Radiopharmaceutical agents are known to be teratogenic.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PBR.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because PBR is a radiopharmaceutical agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to exposure of the mother to PBR, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
- HIV-positive participants are excluded because their immune system is compromised and may affect the interpretation of the imaging data.
- Patients who are not suitable to undergo MRI or PET or use gadolinium contrast due to:
- Claustrophobia
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- Presence of metallic objects or implanted medical devices in body (i.e. cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants) The craniotomy patients will all have titanium but this is MRI compatible
- Sickle cell disease
- Renal failure
- Reduced renal function, as determined by creatinine clearance < 30 mL/min based on a serum creatinine level obtained within 28 days prior to registration
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Massachusetts General Hospital
Boston, Massachusetts, 02215
About this study
This research study is studying the changes in primary and metastatic brain tumor inflammation using positron emission tomography (PET) imaging using a radioactive substance called [11C] PBR28a, which is also known as peripheral benzodiazepine receptors (PBR), or PBR-PET.
Read the detailed description
This research study is a Pilot Study, which is the first time investigators are examining this study intervention. The purpose of a pilot study is to obtain the preliminary data needed to justify performing a larger clinical trial on the effectiveness of an investigational intervention.
Standard treatment for the subjects' disease includes chemoradiation and immunotherapy.
In PET scans, a radioactive substance is injected into the body. The scanning machine finds the radioactive substance, which tends to go to cancer cells and areas of inflammation. For the PET scans in this study, the investigators are using a radioactive substance called [11C]PBR28.
The investigators would like to see if this tracer can be used to detect changes in inflammation during tumor treatment. PBR-PET scans will be performed at screening before therapy and then several weeks/months after the start of therapy, depending on the type of therapy used. No diagnostic decisions or clinical treatment decisions will be made based on any results obtained from these PET scans, and there will be no change in care. The information from these studies may help the investigators design methods that could be used in larger studies to more completely understand the role of inflammation in the treatment of cancer.
- Conditions
- Intracranial Tumors, Glioblastoma, Melanoma
- Being tested
- PBR PET, Cancer Immunotherapy, Radiation and chemotherapy
- Keywords
- Intracranial Tumors, Glioblastoma, Melanoma
- Medical subject headings
- Brain Neoplasms, Glioblastoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBR PETOther
Also called PBR28
Cancer ImmunotherapyBiological
Also called Checkpoint inhibition; Vaccine
Subjects who are to be treated with immunotherapy for glioblastoma or melanoma brain metastases will be eligible for 2 of the 3 arms.
Radiation and chemotherapyRadiation
Also called Chemoradiation
Subjects with glioblastoma will receive or will have received treatment with chemotherapy and radiation per the standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Metastatic Melanoma to the Brain (Cohort A) | Experimental | * Assess Inflammation (PBR PET)
* Immunotherapy
* Assess Inflammation (PBR PET) Receives: Other: PBR PET; Biological: Cancer Immunotherapy |
| Primary Brain Tumor (Cohort B) | Experimental | * Assess Inflammation (PBR PET)
* Immunotherapy
* Assess Inflammation (PBR PET) Receives: Other: PBR PET; Biological: Cancer Immunotherapy |
| Primary Brain Tumor (Cohort C) | Experimental | * Chemoradiation
* Assess inflammation (PBR PET)
* Follow Patients Receives: Other: PBR PET; Radiation: Radiation and chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PBR Uptake (Changes in PBR Uptake by PET)
The change in PBR uptake in arms cohorts A and B from baseline to the start of cycle 4 for metastatic melanoma patients or cycle 3 for glioblastoma patients. The 18-kDa translocator protein (TSPO) is a protein that is expressed in mitochondria and is particularly prominently expressed by activated microglia, infiltrating macrophages, and reactive astrocytes. Thus, it is a marker of neuro-inflammation. PBR28 is a second generation PET tracer that binds to TPSO. PBR28 uptake was quantified using the standardized uptake value (SUV), which is the ratio of activity per unit volume of the region of interest (ROI) compared to cerebellum. Higher values indicate increased uptake in the ROI.
Measured: At baseline and 3 to 4 months post baseline
Median PBR Uptake
The median PBR28 uptake as measured by positron emission tomography (PET) following chemo-radiation. The 18-kDa translocator protein (TSPO) is a protein that is expressed in mitochondria and is particularly prominently expressed by activated microglia, infiltrating macrophages, and reactive astrocytes. Thus, it is a marker of neuro-inflammation. PBR28 is a second generation PET tracer that binds to TPSO. PBR28 uptake was quantified using the standardized uptake value (SUV), which is the ratio of activity per unit volume of the region of interest (ROI) compared to cerebellum. Higher values indicate increased uptake in the ROI.
Measured: At the time of suspected pseudo-progression (up to 4 weeks after consent)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2015 (estimated)
- Study startMay 2015
- Primary completionFeb 2019
- Study completionFeb 2019
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.
- Other trials for Intracranial TumorsStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elizabeth R. Gerstner, MD, Massachusetts General Hospital
- Investigators
- Elizabeth Gerstner, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02431572
- Sponsor's protocol ID
- 14-421
- Status last verified
- Apr 2020
- First submitted
- 15 Apr 2015
- Last updated
- 28 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy
- ClinicalTrials.gov ID
- NCT02431572
- Acronym / sponsor ID
- 14-421
- Conditions
- Intracranial Tumors, Glioblastoma, Melanoma
- Keywords
- Intracranial Tumors, Glioblastoma, Melanoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- May 2015 (actual)
- Primary completion
- Feb 2019 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 1 May 2015 (estimated)
- Results
- Posted 28 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying the changes in primary and metastatic brain tumor inflammation using positron emission tomography (PET) imaging using a radioactive substance called [11C] PBR28a, which is also known as peripheral benzodiazepine receptors (PBR), or PBR-PET.
Detailed description
This research study is a Pilot Study, which is the first time investigators are examining this study intervention. The purpose of a pilot study is to obtain the preliminary data needed to justify performing a larger clinical trial on the effectiveness of an investigational intervention.
Standard treatment for the subjects' disease includes chemoradiation and immunotherapy.
In PET scans, a radioactive substance is injected into the body. The scanning machine finds the radioactive substance, which tends to go to cancer cells and areas of inflammation. For the PET scans in this study, the investigators are using a radioactive substance called [11C]PBR28.
The investigators would like to see if this tracer can be used to detect changes in inflammation during tumor treatment. PBR-PET scans will be performed at screening before therapy and then several weeks/months after the start of therapy, depending on the type of therapy used. No diagnostic decisions or clinical treatment decisions will be made based on any results obtained from these PET scans, and there will be no change in care. The information from these studies may help the investigators design methods that could be used in larger studies to more completely understand the role of inflammation in the treatment of cancer.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Metastatic Melanoma to the Brain (Cohort A) | Experimental | Other: PBR PET, Biological: Cancer Immunotherapy* Assess Inflammation (PBR PET) * Immunotherapy * Assess Inflammation (PBR PET) |
| Primary Brain Tumor (Cohort B) | Experimental | Other: PBR PET, Biological: Cancer Immunotherapy* Assess Inflammation (PBR PET) * Immunotherapy * Assess Inflammation (PBR PET) |
| Primary Brain Tumor (Cohort C) | Experimental | Other: PBR PET, Radiation: Radiation and chemotherapy* Chemoradiation * Assess inflammation (PBR PET) * Follow Patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Participants must have evidence of metastatic melanoma to the brain for Cohort A or histologically confirmed GBM for Cohorts Band C.
- Those with newly diagnosed GBM but suspected to have pseudoprogression after completion of chemoradiation can enroll in Cohort C.
- Participants must have measurable brain disease, defined as at least one lesion that is 10 mm in diameter.
- Age > 18 years.
- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
Key exclusion criteria (10 listed)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PBR.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because PBR is a radiopharmaceutical agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to exposure of the mother to PBR, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
- HIV-positive participants are excluded because their immune system is compromised and may affect the interpretation of the imaging data.
- Patients who are not suitable to undergo MRI or PET or use gadolinium contrast due to:
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 |
|---|---|---|
| PBR PETAlso: PBR28 | Other | Metastatic Melanoma to the Brain (Cohort A), Primary Brain Tumor (Cohort B), Primary Brain Tumor (Cohort C) |
| Cancer ImmunotherapyAlso: Checkpoint inhibition; VaccineSubjects who are to be treated with immunotherapy for glioblastoma or melanoma brain metastases will be eligible for 2 of the 3 arms. | Biological | Metastatic Melanoma to the Brain (Cohort A), Primary Brain Tumor (Cohort B) |
| Radiation and chemotherapyAlso: ChemoradiationSubjects with glioblastoma will receive or will have received treatment with chemotherapy and radiation per the standard of care. | Radiation | Primary Brain Tumor (Cohort C) |
Primary outcome
Change in PBR Uptake (Changes in PBR Uptake by PET)
Time frame: At baseline and 3 to 4 months post baseline
The change in PBR uptake in arms cohorts A and B from baseline to the start of cycle 4 for metastatic melanoma patients or cycle 3 for glioblastoma patients. The 18-kDa translocator protein (TSPO) is a protein that is expressed in mitochondria and is particularly prominently expressed by activated microglia, infiltrating macrophages, and reactive astrocytes. Thus, it is a marker of neuro-inflammation. PBR28 is a second generation PET tracer that binds to TPSO. PBR28 uptake was quantified using the standardized uptake value (SUV), which is the ratio of activity per unit volume of the region of interest (ROI) compared to cerebellum. Higher values indicate increased uptake in the ROI.
Median PBR Uptake
Time frame: At the time of suspected pseudo-progression (up to 4 weeks after consent)
The median PBR28 uptake as measured by positron emission tomography (PET) following chemo-radiation. The 18-kDa translocator protein (TSPO) is a protein that is expressed in mitochondria and is particularly prominently expressed by activated microglia, infiltrating macrophages, and reactive astrocytes. Thus, it is a marker of neuro-inflammation. PBR28 is a second generation PET tracer that binds to TPSO. PBR28 uptake was quantified using the standardized uptake value (SUV), which is the ratio of activity per unit volume of the region of interest (ROI) compared to cerebellum. Higher values indicate increased uptake in the ROI.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Elizabeth Gerstner, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PBR PET, Cancer Immunotherapy and Radiation and chemotherapy in people with Intracranial Tumors and Glioblastoma, run by Massachusetts General Hospital at 2 sites 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 23 inclusion and 10 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 28 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 28 Apr 2020). 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?
Change in PBR Uptake (Changes in PBR Uptake by PET) (time frame: At baseline and 3 to 4 months post baseline). 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 28 Apr 2020.