What side effects are associated with this type of intervention?

Common treatments for prostate cancer include androgen deprivation therapy (ADT), chemotherapy (e.g., docetaxel, cabazitaxel), and radioligand therapies (e.g., lutetium Lu 177 vipivotide tetraxetan). Side effects of ADT can include hot flashes, reduced libido, and osteoporosis. Chemotherapy often leads to fatigue, neutropenia, neuropathy, and alopecia. Radioligand therapies, similar to 225Ac-J591, may cause myelosuppression, nephrotoxicity, and salivary gland toxicity. Each treatment has a unique side effect profile that should be considered when making therapeutic decisions.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that involve radioisotopes and targeted therapies. One notable example is Radium-223 dichloride (Xofigo), which is an alpha-emitting radiopharmaceutical used to treat metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases and no known visceral metastatic disease. Additionally, Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) has been approved for PSMA-positive mCRPC patients who have been previously treated with androgen receptor pathway inhibitors and taxane-based chemotherapy. These treatments, like the Actinium-225 linked antibody therapy being studied in the 225Ac-J591 trial, utilize targeted radiation to destroy cancer cells while minimizing damage to surrounding healthy tissue.

What other types of research exist?

Promising alternatives to 225Ac-J591 for prostate cancer treatment include: 1) Radium-223 dichloride, an alpha emitter targeting bone metastases, which has shown improved survival in phase-3 trials. 2) 177Lu-PSMA-617, a beta-emitting radio-ligand therapy targeting PSMA, which has demonstrated promising results in phase-2 and phase-3 trials. 3) Combination therapies such as Ra-223 with abiraterone or enzalutamide, which have shown potential in nonrandomized studies. 4) PARP inhibitors like rucaparib and niraparib, particularly for patients with HRR gene mutations, which are under investigation in phase-3 trials.

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Radioisotope Therapy

225Ac-J591 Re-treatment for Prostate Cancer

Q: What is the mechanism of action of this treatment?

Prostate cancer treatments often target specific mechanisms to inhibit cancer growth and spread. Targeted alpha-particle therapy, such as 225Ac-J591, uses Actinium-225 linked to an antibody that specifically targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering potent radiation directly to the tumor while sparing surrounding healthy tissue. This precision reduces side effects and enhances efficacy. Other common treatments include androgen deprivation therapy (ADT), which lowers testosterone levels to slow cancer growth, and beta-emitting radioligand therapies like 177Lu-PSMA-617, which also target PSMA but use beta particles for radiation. These targeted approaches are crucial for prostate cancer patients as they offer more effective and personalized treatment options with potentially fewer side effects compared to traditional therapies.

Phase < 1

Waitlist Available

Led By Scott Tagawa, MD

Research Sponsored by Weill Medical College of Cornell University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed adenocarcinoma of prostate

Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: PSA progression, Objective radiographic progression in soft tissue, New bone lesions

Must not have

Radiation therapy ≤4 weeks of Day 1 Cycle 1

Known history of known myelodysplastic syndrome

Timeline

Screening 3 weeks

Treatment Varies

Follow Up will be collected at the time of visit 1 through end of study or 100 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not explicitly listed in the provided information, potential side effects may include typical reactions associated with radioisotope therapies such as nausea, fatigue, blood count changes leading to increased infection risk or bleeding tendencies, kidney damage or other organ-specific issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My prostate cancer was confirmed by a lab test.

Select...

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

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I am taking a medication like abiraterone acetate.

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My testosterone levels are below 50 ng/dL, and I am on hormone therapy or have had an orchiectomy.

Select...

I can take care of myself and am up and about more than half of my waking hours.

Select...

My kidney function, measured by creatinine levels, is within the normal range.

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I am older than 18 years.

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I am taking medication that targets androgen receptors.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

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

Select...

I have been diagnosed with myelodysplastic syndrome.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ will be collected at the time of visit 1 through end of study or 100 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~will be collected at the time of visit 1 through end of study or 100 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and will be collected at the time of visit 1 through end of study or 100 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in the proportion of subjects in assessing safety of 225Ac-J591 in those previously treated with PSMA-TRT.

Secondary study objectives

Change in Overall Survival Following re-Treatment Doses of 225Ac-J591

Change in adverse event rate response

Change in circulating tumor cells (CTC) response

+3 more

Side effects data

From 2023 Phase 1 trial • 32 Patients • NCT03276572

100%

Nausea

100%

Anorexia

100%

Dizziness

100%

Anemia

100%

Fatigue

100%

Xerostomia

100%

Weight loss

100%

Pain

100%

80%

60%

40%

20%

Study treatment Arm

225Ac-J591 Cohort 1

225Ac-J591 Cohort 2

225Ac-J591 Cohort 3

225Ac-J591 Cohort 4

225Ac-J591 Cohort 5

225Ac-J591 Cohort 6

225Ac-J591 Cohort 7

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Moderately ExposedExperimental Treatment1 Intervention

Group II: Heavily ExposedExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

225Ac-J591

2017

Completed Phase 1

~40

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target specific mechanisms to inhibit cancer growth and spread. Targeted alpha-particle therapy, such as 225Ac-J591, uses Actinium-225 linked to an antibody that specifically targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering potent radiation directly to the tumor while sparing surrounding healthy tissue. This precision reduces side effects and enhances efficacy. Other common treatments include androgen deprivation therapy (ADT), which lowers testosterone levels to slow cancer growth, and beta-emitting radioligand therapies like 177Lu-PSMA-617, which also target PSMA but use beta particles for radiation. These targeted approaches are crucial for prostate cancer patients as they offer more effective and personalized treatment options with potentially fewer side effects compared to traditional therapies.

Predictors and Real-World Use of Prostate-Specific Radioligand Therapy: PSMA and Beyond.Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer.225Ac-PSMA-617 for Therapy of Prostate Cancer.