Nanoparticles for Prostate Cancer

Overseen By Karim Touijer, MD, MPH

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Metal implants, Claustrophobia, Renal insufficiency, others

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

Compensation: Varies

Number of Visits: 2

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see whether using the 64Cu-NOTA-PSMA-PEG-Cy5.5-C' dot tracer is a safe way to identify tumor cells before and during surgery for prostate cancer. The researchers want to find out whether PET/MRI scans done after the injection of this investigational tracer are more accurate than the usual imaging scans used to locate deposits of prostate tumor cells. The researchers will study how the tracer travels through your body and where it is distributed. This study is the first time that this tracer will be used in people who are undergoing surgery for prostate cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have certain medical conditions like uncontrolled infections or heart issues, you may not be eligible to participate.

What data supports the effectiveness of the drug 64Cu-NOTA-PSMAi-PEG-Cy5.5-C' dots for prostate cancer?

Research shows that targeting prostate-specific membrane antigen (PSMA) with nanoparticles can improve tumor retention and penetration, leading to better imaging and treatment outcomes. Similar PSMA-targeting agents have demonstrated high tumor uptake and prolonged retention, suggesting potential effectiveness for prostate cancer. ^{1 2 3 4 5}

Is the treatment with 64Cu-labeled PSMA-targeting nanoparticles safe for humans?

The studies on 64Cu-labeled PSMA-targeting nanoparticles, used for imaging prostate cancer, show that they are generally safe in preclinical models, with high stability and specific targeting of cancer cells. However, they do show high uptake in the kidneys and liver, which may require monitoring in human trials. ^{1 6 7 8 9}

How does the nanoparticle treatment for prostate cancer differ from other treatments?

The nanoparticle treatment for prostate cancer is unique because it uses prostate-specific membrane antigen (PSMA) targeting to enhance tumor accumulation and improve imaging and therapeutic efficacy. This approach involves multivalent nanocarriers that penetrate deep into tumor tissues, offering higher tumor retention and lower healthy tissue retention compared to traditional treatments. ^{1 4 5 6 8}

Research Team

Karim Touijer, MD, MPH

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Men over 18 with prostate cancer who are fit for surgery and scheduled for a specific type of operation to remove the prostate or salvage lymph node dissection. They must have certain tumor characteristics like size, shape, or PSA levels. Excluded are those with prior pelvic radiotherapy (except for some cases), weight over 400 lbs, severe claustrophobia, metal implants incompatible with MRI, recent heart issues, kidney problems or uncontrolled infections.

Inclusion Criteria

My doctor thinks I am healthy enough for surgery.

My prostate cancer is advanced, has a high Gleason score, or my PSA level is over 20.

I am 18 years old or older.

Exclusion Criteria

Contraindications to standard-of-care MR imaging (e.g., metal implants, claustrophobia)

I cannot stay still in a scanner for 30 minutes.

I have undergone hormone therapy for prostate cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgery Imaging

Participants receive an intravenous injection of the PSMA-targeting C' dot tracer and undergo serial preoperative PET/MR imaging

Up to 48 hours

1 visit (in-person)

Surgery

Participants undergo surgery for prostate cancer with guidance from imaging results

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including side effects described using CTCAE version 5 criteria

1 year

Treatment Details

Interventions

• (64Cu)-labeled PSMA-targeting particle tracer, or 64Cu-NOTA-PSMAi-PEG-Cy5.5-C' dots

Trial Overview The trial is testing a new tracer called 64Cu-NOTA-PSMAi-PEG-Cy5.5-C' dots during surgery to see if it's better at finding cancer cells than current imaging methods. Participants will undergo PET/MRI scans after receiving this experimental tracer to track its distribution in the body.

Participant Groups

Group I: Prostate cancer patients Experimental Treatment 4 Interventions

Patients will receive an intravenous (IV) injection of approximately 5 mCi (+/- 10%) of PSMAtargeting C' dot tracer up to 48 hours before surgery. Patients will then undergo serial preoperative PET/MR imaging to help characterize the safety, biodistribution/pharmacokinetics, and dosimetry of this agent. To assess total radioactivity in whole blood/plasma and urine samples, as well as radioactive metabolites, blood and urine samples will be collected at approximately 30 min post-injection as well as before each imaging session

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Elucida Oncology

Industry Sponsor

Trials

3

Recruited

90+

Findings from Research

The 64Cu-labeled PSMA tracer, 64Cu-PSMA-CM, shows improved tumor detection capabilities due to its high binding affinity to human serum albumin, which prolongs its half-life in the bloodstream and enhances tumor accumulation.

In comparison to another tracer, 64Cu-PSMA-BCH, 64Cu-PSMA-CM demonstrated significantly higher and prolonged accumulation in PSMA-overexpressing tumors, indicating its potential effectiveness for targeted prostate cancer diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Albumin-Binding PSMA Ligand with Higher Tumor Accumulation for PET Imaging of Prostate Cancer. Ren, Y., Liu, T., Liu, C., et al.[2022]

The newly developed 18F-labeled PSMA-targeting agents, particularly 18F-PEG3-VS-PSMAi, demonstrated significantly higher tumor uptake compared to the FDA-approved 68Ga-PSMA-11, with nearly double the uptake in animal models.

These agents also showed favorable tumor-to-liver ratios, indicating their potential for improved imaging contrast in prostate cancer, suggesting they are promising candidates for further evaluation in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of 18F-Labeled Vinyl Sulfone-PSMAi Conjugates as New PET Agents for Prostate Cancer Imaging. Zhang, T., Cai, J., Xu, M., et al.[2022]

In a study of 24 patients with primary prostate cancer, Ga-PSMA-11 PET/CT demonstrated a high detection rate of 95.8%, confirming its effectiveness in identifying cancerous lesions.

Dynamic PET/CT imaging showed that Ga-PSMA-11 accumulation in prostate cancer lesions increased over time, suggesting its potential for enhancing treatment strategies targeting PSMA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer. Sachpekidis, C., Kopka, K., Eder, M., et al.[2022]

The study developed prostate cancer-targeting starPEG nanocarriers that significantly improved tumor retention and deep tissue penetration compared to nontargeted versions, demonstrating the effectiveness of using prostate-specific membrane antigen (PSMA) targeting.

Multivalent ACUPA ligands on the nanocarriers enhanced binding affinity to prostate cancer cells, leading to better pharmacokinetics and lower retention in healthy tissues, suggesting a promising strategy for improving drug delivery in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate-Specific Membrane Antigen Targeted Deep Tumor Penetration of Polymer Nanocarriers. Meher, N., Ashley, GW., Bidkar, AP., et al.[2023]

The study developed a series of 68Ga/177Lu-labeled PSMA tracers with PEGylation that significantly improved tumor accumulation and reduced kidney retention, enhancing their effectiveness for diagnosing and treating prostate cancer.

Among the tested probes, [68Ga]Ga-DOTA-(2P-PEG4)2 showed superior tumor-targeting ability and prolonged retention in tumor tissues, making it a promising candidate for future clinical applications in prostate cancer imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imageological/Structural Study regarding the Improved Pharmacokinetics by 68Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer. Zhang, H., Rao, M., Zhao, H., et al.[2023]

The radiolabeled ligand [64Cu]PSMA-617 demonstrated high radiochemical purity (>99%) and specific uptake in prostate cancer cells, indicating its potential for effective PET imaging of prostate cancer.

In vivo studies showed that [64Cu]PSMA-617 successfully visualized tumor areas in mice, although it exhibited slow clearance from the kidneys and high uptake in the liver, suggesting that modifications to its structure could enhance its use in imaging and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of [64Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer. Cui, C., Hanyu, M., Hatori, A., et al.[2020]

The study demonstrated that 64Cu labeling of PSMA I&T is highly effective, achieving over 95% labeling yield and maintaining over 90% stability in serum for up to 60 hours, making it a promising candidate for prostate cancer imaging.

In vivo tests showed that 64Cu-PSMA I&T specifically binds to prostate cancer cells (22RV1) significantly better than non-target cells (PC-3), with tumor uptake increasing over time, indicating its potential for effective PET imaging in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Feasibility of 64Cu-PSMA I&T PET for Prostate Cancer. Lee, CH., Lim, I., Woo, SK., et al.[2022]

RPS-085 is a newly developed ligand that effectively targets prostate-specific membrane antigen (PSMA) and shows strong potential for both imaging and treating prostate cancer, with an IC50 of 29 nM indicating its potency as a PSMA inhibitor.

The compound demonstrates favorable pharmacokinetics, with rapid clearance from kidneys and prolonged retention in tumors, suggesting a high therapeutic index for prostate cancer treatment using the radionuclide pair [64/67Cu].

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of a High-Affinity Sarcophagine-Containing PSMA Ligand for 64Cu/67Cu-Based Theranostics in Prostate Cancer. Kelly, JM., Ponnala, S., Amor-Coarasa, A., et al.[2021]

The study demonstrates that 67Cu-CuSarbisPSMA effectively inhibits tumor growth in prostate cancer models, showing similar efficacy to 177Lu-LuPSMA in a dose-dependent manner.

Both single and fractionated doses of 67Cu-CuSarbisPSMA resulted in comparable survival rates, indicating its potential as a viable therapeutic option for patients with PSMA-positive prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Efficacy of a Bivalent Inhibitor of Prostate-Specific Membrane Antigen Labeled with 67Cu. McInnes, LE., Cullinane, C., Roselt, PD., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

An Albumin-Binding PSMA Ligand with Higher Tumor Accumulation for PET Imaging of Prostate Cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Development of 18F-Labeled Vinyl Sulfone-PSMAi Conjugates as New PET Agents for Prostate Cancer Imaging. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Prostate-Specific Membrane Antigen Targeted Deep Tumor Penetration of Polymer Nanocarriers. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Imageological/Structural Study regarding the Improved Pharmacokinetics by 68Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of [64Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

The Feasibility of 64Cu-PSMA I&T PET for Prostate Cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of a High-Affinity Sarcophagine-Containing PSMA Ligand for 64Cu/67Cu-Based Theranostics in Prostate Cancer. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Therapeutic Efficacy of a Bivalent Inhibitor of Prostate-Specific Membrane Antigen Labeled with 67Cu. [2022]