89Zr-cRGDY Tracer for Brain Cancer

Overseen By Heiko Schöder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, Breast-feeding, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for imaging brain tumors using tiny particles called 89Zr-DFO-cRGDY-PEG-Cy5-C' dots, a type of imaging tracer. Researchers aim to observe how these particles spread and exit the body during PET scans, a form of imaging test. This data could enhance future brain cancer treatments. Individuals with a confirmed brain tumor diagnosis and normal heart function may qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to experience this innovative imaging approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that 89Zr-DFO-cRGDY-PEG-Cy5-C' dots are safe for use in humans?

Initial findings suggest that researchers are studying the 89Zr-DFO-cRGDY-PEG-Cy5-C' dots, a new imaging agent, for safety in humans for the first time. Previous research on animals, specifically mice, showed that recovery from tissue effects after a single dose can take up to a year. This implies that while the treatment has potential, its long-term effects in humans remain uncertain.

As this is a Phase 1 study, the main goal is to ensure safety and determine how the body processes these particles. The study uses a much smaller amount of particles than in animal studies, indicating a cautious approach to dosing. This careful strategy aims to minimize risks and monitor how well participants tolerate the treatment.

Currently, no data from human trials indicate specific adverse effects or confirm its safety profile. Participants should consider this and discuss any concerns with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the 89Zr-DFO-cRGDY-PEG-Cy5-C' dots tracer because it offers a novel way to visualize brain cancer. Unlike traditional imaging methods like MRI or CT scans, this tracer targets specific molecules linked to cancer cells, potentially providing more detailed and accurate imaging. This precision could lead to better diagnosis and monitoring of brain tumors. Additionally, the use of zirconium-89 in the tracer allows for longer imaging times, enabling doctors to gather more comprehensive data during PET scans. Overall, these features could make a significant difference in understanding and treating brain cancer.

What evidence suggests that this tracer is effective for brain cancer?

Research has shown that a new type of tiny particle, called 89Zr-DFO-cRGDY-PEG-Cy5-C' dots, could aid in imaging brain tumors. In animal studies, these particles crossed the blood-brain barrier and accumulated in brain tumors, producing clear images. This development is significant as it may enhance doctors' ability to see and understand brain tumors. Early results suggest these particles could improve the accuracy of PET scans, which show how tissues and organs function. In this trial, both non-surgical and surgical patients will receive these particles to evaluate their effectiveness in human brain tumor imaging. Although this marks the first human testing of these particles, their success in targeting brain tumors in animals strongly suggests potential effectiveness. ^{2 6 7 8 9}

Who Is on the Research Team?

Nelson Moss, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed malignant brain tumors, pituitary adenomas, or brain metastases from known cancers. Participants must use birth control if of childbearing age and have normal heart function. Pregnant or breastfeeding individuals, those with multiple active cancers, severe claustrophobia, or weight over 400 lbs cannot join.

Inclusion Criteria

All patients of childbearing age must use an acceptable form of birth control

If you are a woman who has not gone through menopause, you must have a negative pregnancy test.

I have a confirmed diagnosis of a brain tumor or cancer that has spread to my brain.

Exclusion Criteria

I have cancer that has spread from my brain to other parts of my body.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Microdosing Study

Participants receive an intravenous injection of 89Zr-DFO-cRGDY-PEG-Cy5-C' dots and undergo PET brain imaging to collect particle tracer kinetic and dosimetry data

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 89Zr-DFO-cRGDY-PEG-Cy5-C' dots

Trial Overview The study tests a new PET scan tracer called 89Zr-DFO-cRGDY-PEG-Cy5-C' dots to see how well it can image brain tumors and track its distribution and removal in the body. This is the first time these particles are used in humans after being tested in mice.

How Is the Trial Designed?

Group I: surgical patients Experimental Treatment 2 Interventions

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.

Group II: non-surgical patients Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

ADI-PEG20, an arginine-depleting drug, significantly reduces the growth of ASS1 negative glioblastoma multiforme (GBM) tumors in an intracranial model, extending survival without causing obvious toxicity.

When combined with temozolomide, ADI-PEG20 enhances therapeutic effects in both ASS1 negative and ASS1 positive GBM, suggesting a promising treatment strategy that circumvents the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of arginine depletion by ADI-PEG20 in an intracranial model of GBM. Przystal, JM., Hajji, N., Khozoie, C., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6918551/

Nanotechnology in cancer diagnosis: progress, challenges ... ... 89Zr-cRGDY ultrasmall silica particle tracers: a phase 1 microdosing study, Brain cancer, 89Zr-DFO-cRGDY-PEG-Cy5-C' dots, PET imaging, Phase 1 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03465618

NCT03465618 | A First in Human Study Using 89Zr- ... 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.

3. wires.onlinelibrary.wiley.com wires.onlinelibrary.wiley.com/doi/10.1002/wnan.1893

Multi‐ligand functionalized blood‐to‐tumor sequential ... This review summarizes evidences that blood-brain barrier (BBB) and glioblastoma (GBM) sequentially- and dual-targeted nanomedicines, presenting multi-ligand ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6942644/

Ultrasmall Core-Shell Silica Nanoparticles for Precision Drug ... Improvements in brain tumor delivery and penetration, as well as enhancement in the ADR were observed following administration of integrin-targeted C' dots, as ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/26/1/147/82641/Ultrasmall-Core-Shell-Silica-Nanoparticles-for

Ultrasmall Core-Shell Silica Nanoparticles for Precision Drug ... As described previously, the presence of brain tumors was first confirmed via H&E, followed by imaging of 89Zr-cRGD-C' dot accumulation via fluorescence ...

6. trials.braintumor.org trials.braintumor.org/trials/NCT03465618

A First in Human Study Using 89Zr-cRGDY Ultrasmall Silica ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5675572/

Target-or-Clear Zirconium-89 Labeled Silica Nanoparticles ... A control study was performed in M21-L tumor-bearing mice (αvβ3-negative) following injection of 89Zr-DFO-cRGDY-PEG-C′ dots to further demonstrate target ...

8. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/zirconium-zr-89-dfo-crgdy-peg-cy5-c-dots

Definition of zirconium Zr 89-DFO-cRGDY PEG-Cy5-C' dots The fluorescence imaging agent is used to visualize alphaVbeta3-expressing tumor cells and assess the degree of both tumor metastasis and sentinel lymph node ( ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168365920303047

One-year chronic toxicity evaluation of single dose ... This one-year post-exposure evaluation indicate that female and male BALB/c mice need up to one year to recover from acute tissue toxic effects of silica ...