225Ac-J591 Re-treatment for Prostate Cancer

Recruiting at 1 trial location

Overseen By GUONC Research Team

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: Weill Medical College of Cornell University

Must be taking: LHRH/GnRH analogues

Must not be taking: Investigational drugs

Disqualifiers: Active malignancy, DVT/PE, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, 225Ac-J591, which targets and kills prostate cancer cells using radiation. It is aimed at men with advanced prostate cancer that hasn't responded to other treatments. The drug combines a protein that finds cancer cells with a radioactive particle to destroy them. Researchers want to see if it can be given safely without severe side effects. 225Ac-J591 is a new development in PSMA-targeted radiotherapy, building on previous successes with similar treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must continue primary androgen deprivation therapy if you haven't had an orchiectomy (surgical removal of the testicles).

What data supports the effectiveness of the treatment 225Ac-J591 for prostate cancer?

The treatment 225Ac-J591 targets a protein called PSMA, which is found in high levels in most prostate cancers. Similar treatments using 225Ac-PSMA-617 have shown promising results, with some patients experiencing complete responses, indicating the potential effectiveness of 225Ac-J591. ^{1 2 3 4 5}

Is 225Ac-J591 safe for human use?

A study on 225Ac-J591, a treatment for advanced prostate cancer, investigated its safety and found it to be generally safe, but more data is needed to confirm this. Another study on a similar compound, 225Ac-L1, showed some off-target effects, mainly in the kidneys and liver, but it was considered promising for further evaluation. ^{1 2 3 6 7}

What makes the 225Ac-J591 treatment unique for prostate cancer?

The 225Ac-J591 treatment is unique because it uses a monoclonal antibody to specifically target prostate-specific membrane antigen (PSMA) on cancer cells, delivering a powerful alpha radiation directly to the tumor. This approach is different from traditional chemotherapy as it aims to minimize damage to healthy cells and is effective even when other treatments have failed. ^{1 2 3 4 8}

Research Team

Scott Tagawa, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

Men over 18 with advanced prostate cancer that has spread and is resistant to hormone therapy can join. They must have had certain treatments like enzalutamide, abiraterone, or taxane chemotherapy. Good blood counts and organ function are required, and they should be able to perform daily activities with ease to moderate difficulty.

Inclusion Criteria

My prostate cancer was confirmed by a lab test.

I have had taxane chemotherapy, been told I can't have it, or refused it.

My prostate cancer is worsening, shown by rising PSA levels or new cancer spots on scans.

Exclusion Criteria

I had a blood clot in my leg or lung within the last month.

I have not had radiation therapy in the last 4 weeks.

I have been diagnosed with myelodysplastic syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of 225Ac-J591, with potential for a second dose upon progression and tolerance

12 weeks

1 visit (in-person) for each dose

Follow-up

Participants are monitored for safety and effectiveness after treatment, including short-term and long-term follow-up

100 months

Regular visits (in-person) and contact (telephone)

Treatment Details

Interventions

• 225Ac-J591

Trial Overview The trial tests if a second round of the drug 225Ac-J591 for metastatic castration-resistant prostate cancer (mCRPC) can be given safely without causing severe side effects. Participants will have already seen some benefit from this type of treatment before without major toxicities.

Participant Groups

Group I: Moderately Exposed Experimental Treatment 1 Intervention

Group II: Heavily Exposed Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Findings from Research

The study of 32 patients with metastatic castration-resistant prostate cancer (mCRPC) showed that the radiolabeled antibody 225Ac-J591 is safe, with a maximum tolerated dose not reached and only one patient experiencing dose-limiting toxicity.

Preliminary efficacy results indicated that 46.9% of patients had at least a 50% decline in prostate-specific antigen (PSA) levels, and 59.1% showed a response in circulating tumor cell counts, suggesting potential effectiveness of this novel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591. Tagawa, ST., Thomas, C., Sartor, AO., et al.[2023]

In a first-in-human trial, two patients with advanced prostate cancer showed a complete response to treatment with 225Ac-PSMA-617, indicating its potential efficacy as a targeted therapy.

The treatment resulted in a significant decline in prostate-specific antigen levels without relevant hematologic toxicity, suggesting a favorable safety profile, with xerostomia being the only notable side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer. Kratochwil, C., Bruchertseifer, F., Giesel, FL., et al.[2022]

Targeted alpha therapy using 225Ac-labeled PSMA-617 has shown remarkable therapeutic efficacy in treating metastatic castration-resistant prostate cancer, highlighting its potential as a treatment option.

The review also discusses the production methods for 225Ac and its daughter nuclide 213Bi, along with clinical experiences in using these alpha emitters for various cancers, including bladder cancer and brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of Targeted Alpha Therapy with 225Actinium and 213Bismuth. Morgenstern, A., Apostolidis, C., Kratochwil, C., et al.[2019]

The new α-particle-emitting compound 225Ac-L1 shows specific targeting and effective cell kill in prostate cancer cells that express PSMA, demonstrating significant tumor growth inhibition and improved survival in xenograft models.

While 225Ac-L1 has promising efficacy, it also presents some off-target radiotoxicity, particularly in the kidneys and liver, with a maximum tolerated dose estimated at about 1 MBq/kg, indicating a need for careful dosing in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of 213Bi- and 225Ac-Labeled Low-Molecular-Weight Compounds for Radiopharmaceutical Therapy of Prostate Cancer. Banerjee, SR., Lisok, A., Minn, I., et al.[2022]

The FDA has approved 177Lu-PSMA-617 for treating advanced metastatic castrate-resistant prostate cancer (mCRPC), marking a significant advancement in PSMA-targeted therapies.

Various PSMA-targeted radiopharmaceuticals, including both beta and alpha emitters, are in development, with promising results for alpha therapies like 225Ac-PSMA-617, although there are concerns about potential toxicity to salivary and renal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts. Sartor, O., Baghian, A.[2022]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy of Metastatic Prostate Cancer with ¹⁷⁷Lu-DOTAhuJ591 Anti Prostate Specific Membrane Antigen Specific Monoclonal Antibody. [2019]

2. Turkey pubmed.ncbi.nlm.nih.gov

Relative Efficacy of 225Ac-PSMA-617 and 177Lu-PSMA-617 in Prostate Cancer Based on Subcellular Dosimetry. [2022]

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

Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591. [2023]

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

225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer. [2022]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

An Overview of Targeted Alpha Therapy with 225Actinium and 213Bismuth. [2019]

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

Preclinical Evaluation of 213Bi- and 225Ac-Labeled Low-Molecular-Weight Compounds for Radiopharmaceutical Therapy of Prostate Cancer. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts. [2022]

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

Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate cancer. [2021]