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

NCT02431572 | Completed Results DMC

• 1 other identifier: 14-421
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Intracranial Tumors; Glioblastoma; Melanoma

Keywords

Intracranial Tumors; Glioblastoma; Melanoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  At the time of suspected pseudo-progression (up to 4 weeks after consent)

Study Arms (3)

Metastatic Melanoma to the Brain (Cohort A)

EXPERIMENTAL

* Assess Inflammation (PBR PET) * Immunotherapy * Assess Inflammation (PBR PET)

Other: PBR PET; Biological: Cancer Immunotherapy

Primary Brain Tumor (Cohort B)

EXPERIMENTAL

* Assess Inflammation (PBR PET) * Immunotherapy * Assess Inflammation (PBR PET)

Other: PBR PET; Biological: Cancer Immunotherapy

Primary Brain Tumor (Cohort C)

EXPERIMENTAL

* Chemoradiation * Assess inflammation (PBR PET) * Follow Patients

Other: PBR PET; Radiation: Radiation and chemotherapy

Interventions

PBR PET OTHER

Also known as: PBR28

Metastatic Melanoma to the Brain (Cohort A); Primary Brain Tumor (Cohort B); Primary Brain Tumor (Cohort C)

Cancer Immunotherapy BIOLOGICAL

Subjects who are to be treated with immunotherapy for glioblastoma or melanoma brain metastases will be eligible for 2 of the 3 arms.

Also known as: Checkpoint inhibition; Vaccine

Metastatic Melanoma to the Brain (Cohort A); Primary Brain Tumor (Cohort B)

Radiation and chemotherapy RADIATION

Subjects with glioblastoma will receive or will have received treatment with chemotherapy and radiation per the standard of care.

Also known as: Chemoradiation

Primary Brain Tumor (Cohort C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma; Melanoma

Interventions

Vaccines; Radiation; Drug Therapy; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Physical Phenomena; Therapeutics; Combined Modality Therapy; Radiotherapy

Results Point of Contact

• Title: Dr. Elizabeth Gerstner
• Organization: Massachusetts General Hospital

EGERSTNER@mgh.harvard.edu

617-724-8770

Study Officials

• Elizabeth Gerstner, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigators

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: May 1, 2015
• Study Start: May 1, 2015
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: April 28, 2020
• Results First Posted: April 28, 2020

Record last verified: 2020-04

Locations

US (2)