177Lu-PSMA-617 for Prostate Cancer

(PRODIGY-2 Trial)

Recruiting at 1 trial location

Overseen By Marie-Christine Dubé, Ph.D.

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Jean-Mathieu Beauregard

Disqualifiers: Active malignancy, CNS metastasis, others

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

Compensation: Varies

Number of Visits: 6

Duration: 36 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating prostate cancer that has spread and no longer responds to standard hormone therapy. It examines whether a personalized dose of 177Lu-PSMA-617 (a type of radioligand therapy) can be safely increased for better results compared to the usual fixed dose. Researchers aim to determine if this personalized approach leads to more side effects or if patients can handle it well. Men with prostate cancer that worsens despite treatment and who have specific cancer markers seen in scans might be suitable for this study. Participants will receive up to six treatments every six weeks and undergo regular check-ups to monitor progress and side effects. 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 receive this new therapy.

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.

Is there any evidence suggesting that 177Lu-PSMA-617 is likely to be safe for humans?

Studies have shown that 177Lu-PSMA-617, a targeted treatment for prostate cancer, is generally safe for patients. Research indicates it can extend patients' lives and slow disease progression. For example, one study found that adding this treatment to standard care extended patients' lives and delayed cancer's spread.

Regarding side effects, long-term safety data is still being collected, but early results are encouraging. Some studies have reported similar safety outcomes when comparing 177Lu-PSMA-617 with other treatments. Most patients tolerate it well, though monitoring for potential issues over time remains important.

This treatment is already used in some prostate cancer cases, suggesting a certain level of safety. However, since this trial is in an early phase, researchers are still confirming its full safety profile. Participants will be closely monitored for any adverse reactions, especially as this study explores personalized doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Most treatments for prostate cancer, like hormone therapy and chemotherapy, aim to slow or stop cancer growth, but 177Lu-PSMA-617 works differently. It targets a specific protein on prostate cancer cells called PSMA and delivers a radioactive particle directly to the cancer, potentially minimizing damage to healthy tissues. Researchers are excited about this treatment because it offers a more personalized approach, with one arm of the study testing personalized activity levels, which could lead to better outcomes by tailoring the radiation dose to the individual patient's needs. This innovative method might improve effectiveness and reduce side effects compared to traditional treatments.

What evidence suggests that 177Lu-PSMA-617 might be an effective treatment for prostate cancer?

Research has shown that 177Lu-PSMA-617 is a promising treatment for advanced prostate cancer that no longer responds to hormone therapy. In this trial, participants will receive either a personalized activity or a fixed activity of 177Lu-PSMA-617. Studies have found that this treatment can significantly reduce prostate-specific antigen (PSA) levels, with more than half of the patients experiencing a drop of over 50% in PSA levels. This indicates effective cancer fighting. Additionally, about half of the patients showed positive results in imaging tests, with some having complete or partial improvements. The treatment delivers radiation directly to cancer cells with a specific marker, potentially killing them. These findings suggest that 177Lu-PSMA-617 could be a strong treatment option for patients with this type of prostate cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Jean-Mathieu Beauregard, MD

Principal Investigator

CHU de Québec-Université Laval

Are You a Good Fit for This Trial?

This trial is for patients with metastatic castrate-resistant prostate cancer. Participants will be considered if they can undergo up to 6 treatments every 6 weeks and are able to have their radiation delivery to the kidneys measured.

Inclusion Criteria

Signed, written informed consent

PSA ≥2 ng/mL

Calculated eGFR (by CKD-EPI formula) ≥ 45 mL/min/1.73m^2

Exclusion Criteria

I have had radiopharmaceutical therapy before.

Any other condition, diagnosis or finding that may in the investigator's opinion interfere with trial conduct

My scans show extensive cancer spread to bones.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 6 treatments of 177Lu-PSMA-617 every 6 weeks, evaluated with imaging, laboratory tests, and questionnaires

36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term follow-up

Participants are monitored for delayed adverse events and overall survival

60 months

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-617

Trial Overview

The study tests whether a personalized dosage of the radiopharmaceutical therapy, 177Lu-PSMA-617, based on kidney dosimetry, is more effective and safe compared to a standard fixed dose in treating prostate cancer.

How Is the Trial Designed?

Group I: Personalized activity Experimental Treatment 1 Intervention

Group II: Fixed activity Active Control 1 Intervention

Who Is Running the Clinical Trial?

Jean-Mathieu Beauregard

Lead Sponsor

CHU de Quebec-Universite Laval

Collaborator

Trials

177

Recruited

110,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

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

Published Research Related to This Trial

The study successfully prepared a patient dose of (177)Lu-labeled PSMA-617 with over 98% radiochemical purity, indicating a high-quality formulation for potential use in prostate cancer treatment.

Preliminary clinical investigations in 7 prostate cancer patients showed that (177)Lu-labeled PSMA-617 had a distribution pattern similar to that of diagnostic (68)Ga-PSMA-11 PET scans, suggesting its potential for theranostic applications, although further studies with larger patient groups are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical translation of (177)Lu-labeled PSMA-617: Initial experience in prostate cancer patients. Das, T., Guleria, M., Parab, A., et al.[2021]

In a phase I/II trial involving 20 men with high-risk localized prostate cancer, treatment with [177Lu]Lu-PSMA-617 delivered high radiation doses to tumors with minimal side effects, indicating its safety prior to surgery.

The treatment resulted in a significant PSA decline in 45% of patients, suggesting potential efficacy in reducing tumor burden before radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study. Eapen, RS., Buteau, JP., Jackson, P., et al.[2023]

[177Lu]Lu-PSMA-617 is effective in targeting prostate cancer, but some patients do not respond well; ongoing research is exploring combination therapies to improve outcomes for both treatment-naïve and resistant patients.

Combining [177Lu]Lu-PSMA-617 with other treatments, such as alpha radiation emitters and immune checkpoint inhibitors, shows promise in enhancing therapeutic responses, particularly for patients who have developed resistance to initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. Arbuznikova, D., Eder, M., Grosu, AL., et al.[2023]

In a phase II trial, the novel radiopharmaceutical 177Lu-PSMA-617 demonstrated a significantly higher prostate-specific antigen (PSA) response in men with metastatic castration-resistant prostate cancer, with 66% of patients showing a response compared to only 37% in those treated with chemotherapy (cabazitaxel).

This suggests that 177Lu-PSMA-617 may be a more effective treatment option than traditional chemotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radionuclide Reduces PSA in mCRPC. [2021]

In a study involving 145 patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with 177Lu-PSMA-617 showed a biochemical response rate of 45%, indicating high efficacy, especially with 40% of patients responding after just one treatment cycle.

The therapy demonstrated a favorable safety profile, with only 10% of patients experiencing severe hematotoxicity and 8% reporting dry mouth, suggesting it may be a safer option compared to other third-line treatments for mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. Rahbar, K., Ahmadzadehfar, H., Kratochwil, C., et al.[2022]

177Lu-PSMA-617 therapy has shown promising efficacy in treating metastatic prostate cancer, with a majority of patients experiencing a decline in prostate-specific antigen (PSA) levels, which is associated with longer survival rates.

The analysis of 17 studies indicated that while significant toxicities were infrequent, cytopenias were noted, and factors like performance status and tumor grade were important predictors of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. Sun, M., Niaz, MO., Nelson, A., et al.[2020]

In a study of 50 men with advanced prostate cancer, 177Lu-PSMA-617 demonstrated a 64% rate of PSA decline of at least 50%, indicating its efficacy in targeting prostate-specific membrane antigen for treatment.

The treatment was associated with low toxicity, with common side effects being mild and self-limiting, and patients reported improved quality of life, with median overall survival reaching 13.3 months, particularly benefiting those who achieved significant PSA reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Violet, J., Sandhu, S., Iravani, A., et al.[2022]

In a study of 10 patients with high-volume metastatic hormone-sensitive prostate cancer, 177 Lu-PSMA-617 treatment resulted in 50% of patients achieving an undetectable PSA level, indicating effective disease control.

The treatment demonstrated a median radiographic progression-free survival of 24 months, with no severe adverse events reported, suggesting that 177 Lu-PSMA-617 is both safe and effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promising Therapeutic Activity of 177Lu-PSMA-617 in Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer: A Pilot Experience. Satapathy, S., Yadav, MP., Ballal, S., et al.[2023]

177Lu-PSMA-617 is a promising new treatment for patients with advanced prostate cancer, specifically targeting the prostate-specific membrane antigen (PSMA) found on cancer cells.

The therapy was also experimentally applied to a female patient with metastasized leiomyosarcoma, suggesting potential for PSMA-targeted treatment in other types of tumors beyond prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. Jüptner, M., Marx, M., Zuhayra, M., et al.[2021]

In a study involving 64 patients with metastatic castration-resistant prostate cancer, 177Lu-PSMA-617 was found to be safe and well-tolerated, with manageable side effects such as dry mouth, fatigue, and nausea occurring in a significant number of patients.

The treatment did not lead to serious adverse events directly related to the drug, and there were no significant changes in vital signs or kidney function, suggesting a favorable safety profile for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). Calais, J., Czernin, J., Thin, P., et al.[2023]

177Lu-DKFZ-PSMA-617 is a safe and promising treatment for patients with metastatic prostate cancer, with individualized dosimetry calculations showing specific absorbed doses for organs like kidneys and salivary glands.

The study involved 10 patients with a mean age of 71.4 years, highlighting significant inter-individual variations in organ dose, which underscores the importance of personalized treatment planning for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Specific Dosimetry in Radioligand Therapy (RLT) for Metastatic Prostate Cancer Using 177Lu-DKFZ-PSMA-617. Mahmoudi, E., Pirayesh, E., Deevband, MR., et al.[2022]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2107322

Lutetium-177–PSMA-617 for Metastatic Castration ...

Lutetium-177 ( 177 Lu)–PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37818966/

The real-world outcomes of Lutetium-177 PSMA-617 ...

The Lu-177 PSMA-617 RLT led to a significant PSA response, with 50.6% of patients achieving a >50% decrease in PSA levels. Median overall ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.82

Survival outcomes of patients (pts) with metastatic ...

Characteristics and outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177–PSMA-617 ( ...

4.

jnm.snmjournals.org

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

Outcomes of [177Lu] Lu-PSMA-617 Re-Treatment in ...

A favorable imaging response was observed in 10 patients (50%, 10/20), with 4 achieving a complete response and 6 achieving a partial response, ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0302283824026083

A Meta-Analysis and Meta-Regression of the Efficacy ...

In some studies, [177Lu]Lu-PSMA therapy has been shown to decrease the level of prostate-specific antigen (PSA) by at least 50%, with a favourable toxicity ...

6.

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 ...

7.

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 ...

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.

9.

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 ...