A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy

April 20, 2020 updated by: Elizabeth R. Gerstner, MD, Massachusetts General Hospital
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

11

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02215
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

  • 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.

Exclusion Criteria:

  • 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
    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Metastatic Melanoma to the Brain (Cohort A)
  • Assess Inflammation (PBR PET)
  • Immunotherapy
  • Assess Inflammation (PBR PET)
Other: PBR PET
Other Names:
  • PBR28
Biological: Cancer Immunotherapy
Subjects who are to be treated with immunotherapy for glioblastoma or melanoma brain metastases will be eligible for 2 of the 3 arms.
Other Names:
  • Checkpoint inhibition; Vaccine
Experimental: Primary Brain Tumor (Cohort B)
  • Assess Inflammation (PBR PET)
  • Immunotherapy
  • Assess Inflammation (PBR PET)
Other: PBR PET
Other Names:
  • PBR28
Biological: Cancer Immunotherapy
Subjects who are to be treated with immunotherapy for glioblastoma or melanoma brain metastases will be eligible for 2 of the 3 arms.
Other Names:
  • Checkpoint inhibition; Vaccine
Experimental: Primary Brain Tumor (Cohort C)
  • Chemoradiation
  • Assess inflammation (PBR PET)
  • Follow Patients
Other: PBR PET
Other Names:
  • PBR28
Radiation: Radiation and chemotherapy
Subjects with glioblastoma will receive or will have received treatment with chemotherapy and radiation per the standard of care.
Other Names:
  • Chemoradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At baseline and 3 to 4 months post baseline
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.
At the time of suspected pseudo-progression (up to 4 weeks after consent)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Elizabeth Gerstner, MD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2015

Primary Completion (Actual)

February 1, 2019

Study Completion (Actual)

February 1, 2019

Study Registration Dates

First Submitted

April 15, 2015

First Submitted That Met QC Criteria

April 30, 2015

First Posted (Estimate)

May 1, 2015

Study Record Updates

Last Update Posted (Actual)

April 28, 2020

Last Update Submitted That Met QC Criteria

April 20, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-421

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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