A First in Human Study Using 89Zr-cRGDY Ultrasmall Silica Particle Tracers for Malignant Brain Tumors

Study Overview
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Brief Summary
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The purpose of this study is to test if PET scans using 89Zr-DFO-cRGDY-PEG-Cy5-C' dot particles, can be used to take pictures of brain tumors. The investigators want to understand how the particles are distributed and removed from the body, which may help others be treated in the future. This will be the first time that 89Zr-DFO-cRGDY-PEG-Cy5-C' dot particles are being used in people. The amount of particles given in this study is very small compared to the amount that was used in mice animal studies.

Official Title
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Imaging of Patients With Malignant Brain Tumors Using 89Zr-cRGDY Ultrasmall Silica Particle Tracers: A Phase 1 Microdosing Study

Conditions
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Brain Cancer, Pituitary Adenoma

Intervention / Treatment
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* Drug: 89Zr-DFO-cRGDY-PEG-Cy5-C' dots PET Imaging
* Other: Blood and Urine samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Histologically confirmed diagnosis of malignant primary brain tumor clinical and radiographic findings consistent with a pituitary adenoma, or known metastatic cancer with brain lesion presumed to be metastatic. Normal baseline cardiac function based upon pre-operative evaluation at the physcian's discretion All patients of childbearing age must use an acceptable form of birth control Women who are pre-menopausal must have a negative serum pregnancy test Exclusion Criteria: Known pregnancy or breast-feeding Medical illness unrelated to the tumor which in the opinion of the attending physician and principal investigator will preclude administration of the tracer °This includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis, or New York Heart Association Classification III or IV heart disease More than one metastatic cancer active in the last 5 years Active metastatic cancer in addition to malignant primary brain tumor Weight greater than the 400-lb weight limit of the PET scanner Unmanageable claustrophobia Inability to lie in the scanner for 30 minutes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a two-year microdosing study that will enroll up to 10 surgical or non-surgical patients harboring pituitary adenomas, high grade gliomas or metastatic brain tumors.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: surgical patients<br>Patients will be i.v. injected with approximately 5 mCi ( 3.4-6.7 nanomoles) of 89Zr-DFO-cRGDY-PEG-Cy5-C' dots (specific activity range 750.0 - 1450 mCi/ µmol) and undergo the microdosing study for purposes of collecting particle tracer kinetic and dosimetry data. The patient's PET/CT Brain scans may be acquired prior to surgery. All non-surgical and some surgical patients (at the discretion of the physician) will undergo PET brain imaging. | Drug: 89Zr-DFO-cRGDY-PEG-Cy5-C' dots PET Imaging<br>* A low dose spiral CT is performed first per the standard procedure. These images will be used for both attenuation correction and registration of the serial image set. The initial PET brain scan will be acquired up to about 24 hours post injection. Based upon the discretion of the physician, non-surgical patients have the possibility of a second scan and third up to about 48 hours post injection. The times per bed position may be adjusted after the first patient is imaged, and his/her scans evaluated. Additional low dose CT scans will be performed at the image session for attenuation correction and image registration. PET study may be done on a PET-MR scanner for ease.<br>Other: Blood and Urine samples<br>* Venous blood and urine samples will be obtained at approximately 0.5 hours post injection at the end of each scan<br>|
| Experimental: non-surgical patients<br>Before the patient's PET Brain scans patients will be i.v. injected with approximately 5 mCi ( 3.4-6.7 nanomoles) of 89Zr-DFO-cRGDY-PEG-Cy5-C' dots (specific activity range 750.0 - 1450 mCi/ µmol) and undergo the microdosing study for purposes of collecting particle tracer kinetic and dosimetry data. All non-surgical and some surgical patients (at the discretion of the physician) will undergo PET brain imaging | Drug: 89Zr-DFO-cRGDY-PEG-Cy5-C' dots PET Imaging<br>* A low dose spiral CT is performed first per the standard procedure. These images will be used for both attenuation correction and registration of the serial image set. The initial PET brain scan will be acquired up to about 24 hours post injection. Based upon the discretion of the physician, non-surgical patients have the possibility of a second scan and third up to about 48 hours post injection. The times per bed position may be adjusted after the first patient is imaged, and his/her scans evaluated. Additional low dose CT scans will be performed at the image session for attenuation correction and image registration. PET study may be done on a PET-MR scanner for ease.<br>Other: Blood and Urine samples<br>* Venous blood and urine samples will be obtained at approximately 0.5 hours post injection at the end of each scan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| distribution within these high-grade gliomas | using serial PET imaging and/or correlative histologyFollowing tumor biopsy or surgical resection, histologic assessments will be performed using autoradiography to visualize the distribution of this agent within tumor tissue specimens. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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89Zr-cRGDY Ultrasmall Silica Particle Tracers, Pet Scan, 17-599