177Lu-PSMA-617 vs 225Ac-PSMA-617 for Prostate Cancer

(LUTACT Trial)

Overseen By Maya Aslam

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Thomas Hope

Must not be taking: 5-alpha reductase inhibitors

Disqualifiers: Prior prostate cancer therapy, others

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

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments to determine which more effectively targets prostate cancer cells before surgery. Participants will receive either 177Lu-PSMA-617 or 225Ac-PSMA-617, both therapies that deliver radiation directly to cancer cells. The aim is to discover which treatment is more effective and how they differ in their effects on cancer. The trial seeks men with high-risk localized prostate cancer who plan to undergo prostate surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these innovative therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that prior prostate cancer therapy is not allowed, and certain medications like 5-alpha reductase inhibitors must be stopped at least 3 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both 177Lu-PSMA-617 and 225Ac-PSMA-617 have been tested for safety in humans, particularly for prostate cancer treatment. Patients generally tolerate 177Lu-PSMA-617 well. Studies have found that side effects like dry mouth and tiredness are usually manageable. Importantly, this treatment is already used in some prostate cancer cases, supporting its safety to some degree.

Similarly, researchers are studying 225Ac-PSMA-617 for safety. Research suggests it is generally safe with few side effects for most patients. Common side effects include mild tiredness and reduced appetite. Overall, evidence indicates that both treatments have been safe for many people who have used them. However, as this trial is in its early stages, detailed safety information is still being gathered. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 177Lu-PSMA-617 and 225Ac-PSMA-617 treatments for prostate cancer because they target prostate-specific membrane antigen (PSMA) with radioligands, which is different from traditional treatments like surgery, hormone therapy, or chemotherapy. These radioligands deliver radioactive particles directly to cancer cells, minimizing damage to healthy tissue. The use of lutetium-177 and actinium-225 as active ingredients offers distinct benefits; lutetium-177 is known for its ability to emit beta particles, while actinium-225 emits alpha particles, potentially providing a more powerful and precise attack on cancer cells. This targeted approach could lead to more effective treatments with fewer side effects compared to current standard therapies.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will compare 177Lu-PSMA-617 and 225Ac-PSMA-617 for treating prostate cancer. Research has shown that 177Lu-PSMA-617 yields promising results, with good response rates, less pain, and low side effects. Participants in one arm of this trial will receive 177Lu-PSMA-617. For 225Ac-PSMA-617, research indicates it controls the disease well with few side effects, and some patients have lived longer and experienced a better quality of life. Participants in another arm of this trial will receive 225Ac-PSMA-617. Both treatments target specific proteins on prostate cancer cells, delivering radiation directly to them. Early evidence suggests that 225Ac-PSMA-617 might be more effective than 177Lu-PSMA-617. ^{1 2 6 7 8}

Who Is on the Research Team?

Thomas A Hope, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals with high or very high risk localized or locoregional prostate cancer who are planning to have their prostate removed (prostatectomy). Specific eligibility criteria details were not provided.

Inclusion Criteria

Ability to understand and sign a written informed consent document

Consent to comply with recommended radioprotection precautions

Use of adequate contraception and refraining from sperm donation during and after the study period

Exclusion Criteria

Participation in a study involving investigational products within four weeks of treatment

Concurrent serious medical conditions as determined by the principal investigator

Severe atherosclerosis or significant smoking history for participants undergoing intraarterial administration of PSMA RLT

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1 to 2 cycles of PSMA radioligand therapy up to 6 weeks apart before a scheduled prostatectomy

6 weeks

1-2 visits (in-person)

Prostatectomy

Participants undergo a scheduled, non-investigational prostatectomy four weeks after completing radioligand therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including safety assessment 6 weeks after surgery and long-term follow-up

60 months

Multiple visits (in-person and virtual) at 3, 6, 12, and 60 months

What Are the Treatments Tested in This Trial?

Interventions

• 177 Lutetium Prostate-Specific Membrane Antigen 617
• Actinium-225 Prostate-Specific Membrane Antigen 617

Trial Overview The study compares two radioligand therapies: Actinium-225 Prostate-Specific Membrane Antigen (225Ac-PSMA) and Lutetium-177 Prostate-Specific Membrane Antigen (177Lu-PSMA), in a single center, pilot study format. It aims to assess the differences in mechanisms of these treatments before patients undergo prostatectomy.

How Is the Trial Designed?

Group I: Control Group (Prostatectomy only) Experimental Treatment 3 Interventions

Participants will obtain a non-investigational prostatectomy. Tumor tissue obtained at the time of surgery will be utilized for comparisons with the cohorts receiving study therapies. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and up to 24 months after surgery.

Group II: Cohort 2 (225Ac-PSMA-617) Experimental Treatment 5 Interventions

Five participants will receive a single dose of 225Ac-PSMA-617 radioligand therapy IV, five participants will receive a single dose of 225Ac-PSMA-617 IA, and five participants will receive two doses over 6 weeks IV. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, and 60 months for long-term outcomes.

Group III: Cohort 1 (177Lu-PSMA-617) Experimental Treatment 5 Interventions

Five participants will receive a single dose of 177Lu-PSMA-617 radioligand therapy intravenously (IV), five participants will receive a single dose of 177Lu-PSMA-617 intra-arterially (IA), and five participants will receive two doses over 6 weeks intravenously. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, and 60 months for long-term outcomes.

Who Is Running the Clinical Trial?

Thomas Hope

Lead Sponsor

Trials

11

Recruited

1,800+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107322

Lutetium-177–PSMA-617 for Metastatic Castration ... This radioligand therapy has been associated with encouraging biochemical and radiographic response rates, reduced pain, and low toxicity in multiple early- ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40752988/

Outcomes for [ 177 Lu]Lu-PSMA-617 with and Without ... Key findings and limitations: Among 256 patients, 106 (41.4%) received an ARPI with [177Lu]Lu-PSMA-617. Those receiving an ARPI had lower ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251923

Outcomes of [177Lu] Lu-PSMA-617 Re-Treatment in ... Results: A total of 589 patients underwent [177Lu] Lu-PSMA-617 RLT, of whom 20 (3.4%, 20/589) received RLT retreatment. The median age was 71.3 ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.112

Outcomes for 177Lu-PSMA-617 with and without ... Patients receiving an ARPI with 177 Lu-PSMA-617 were more likely to complete all 6 cycles of treatment, but no clear differences in survival were observed on ...

5. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)01653-2/abstract

177Lu-PSMA-617 versus a change of androgen receptor ... The incidence of grade 3–5 adverse events was lower in the 177Lu-PSMA-617 group (at least one event in 81 [36%] of 227 patients; four [2%] grade ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS294

Long-term safety outcomes of 177Lu-PSMA-617 in patients ... It is important to further characterize long-term safety outcomes in 177 Lu-PSMA-617–treated patients, with particular regard to potential treatment-related ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00852-X/fulltext

Final overall survival and safety analyses of the phase III ... At the time of the final OS analysis, 299 deaths were reported in 142/234 participants (60.7%) in the 177Lu-PSMA-617 arm and 157/234 (67.1%) in ...

8. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251339

Comparative Safety and Efficacy of 177Lu-PSMA-617 and ... In this first comparative analysis of 177 Lu-PSMA-617 and 177 Lu-PSMA-I&T RLT in Taiwanese mCRPC patients, both agents demonstrated similar safety and efficacy.