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

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.

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