Lu 177 for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Investigational agents

Disqualifiers: Active malignancy, Infection, Psychiatric illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 30-36 weeks

236 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness of Lu 177, a type of radioligand therapy using radioactive particles, for treating prostate cancer that has spread and resists standard hormone treatments. Researchers are comparing two approaches: administering the treatment for 5 cycles with a pause versus the usual continuous 6 cycles. The goal is to determine if the pause can lead to better treatment outcomes. Suitable participants have prostate cancer that does not respond to hormone therapy and has metastasized. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that Lutetium Lu 177 vipivotide tetraxetan is generally well-tolerated by patients with prostate cancer. In one study, about 68.9% of participants experienced a significant improvement in their PSA levels, an important indicator of prostate cancer activity.

While the treatment appears promising, some patients experienced side effects, including fatigue, dry mouth, nausea, and low blood cell counts, which are common with cancer treatments. However, serious side effects were rare. Only a small number of patients had severe reactions, indicating that most people can handle the treatment well.

The treatment also has approval for other uses, providing an extra level of safety assurance. This approval means it has passed strict testing to meet safety standards. Overall, the evidence suggests Lutetium Lu 177 is a safe option for treating prostate cancer, with side effects that most patients can manage. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about Lutetium Lu 177 Vipivotide Tetraxetan for prostate cancer because it offers a targeted radioligand therapy, which is different from current options like chemotherapy or hormonal therapies. This treatment uses a radioactive compound that specifically targets PSMA, a protein commonly found in high levels on prostate cancer cells, delivering radiation directly to the cancer while sparing healthy tissue. Additionally, the trial explores different treatment strategies, such as pausing treatment until progression, which could optimize effectiveness and minimize side effects. By potentially providing more precise targeting and innovative treatment scheduling, this approach could improve outcomes for patients with advanced prostate cancer.

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

Research has shown that Lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) may help treat advanced prostate cancer that no longer responds to hormone therapy. Studies have found that it can extend patients' lives, with an average survival time of 15.3 months. Additionally, about 69% of patients experienced a significant drop in their PSA levels, a marker used to monitor prostate cancer, with some cases showing a reduction of 50% or more. This trial will evaluate 177Lu-PSMA-617 in different treatment arms, including standard administration and treatment pause strategies. This treatment also reduces the risk of cancer progression or death compared to standard care alone. Overall, these findings suggest that 177Lu-PSMA-617 could be a promising option for patients with advanced prostate cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Matthew P. Thorpe, M.D., Ph.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for patients with metastatic castrate-resistant prostate cancer. Participants should have a type of tumor that can be targeted by the drug being tested. The specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

My kidney function is low, with a GFR under 30 mL/min.

First progression in patients randomized to pause treatment

Willingness to provide mandatory blood draws for correlative research

Exclusion Criteria

Receiving any other investigational agent for prostate cancer

I have experienced a serious side effect from treatment.

I am currently being treated for another cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 177Lu-PSMA-617 intravenously over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 or 6 cycles depending on the arm, in the absence of disease progression or unacceptable toxicity.

30-36 weeks

6 visits (in-person)

Observation

Participants undergo clinical observation until documented first progression.

Variable, until progression

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 12 weeks for up to 2 years or until progressive disease.

Up to 2 years

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177 Vipivotide Tetraxetan

Trial Overview The study is testing whether giving a radioactive drug called Lutetium Lu 177 Vipivotide Tetraxetan (177Lu-PSMA-617) for five treatment cycles is as effective as the standard six cycles in treating prostate cancer that has spread.

How Is the Trial Designed?

Group I: Arm III (Treatment pause 177Lu-PSMA-617) Experimental Treatment 9 Interventions

Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

Group II: Arm II (177Lu-PSMA-617 treatment pause) Experimental Treatment 9 Interventions

Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

Group III: Arm I (177Lu-PSMA-617 standard) Active Control 8 Interventions

Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

Lutetium Lu 177 Vipivotide Tetraxetan is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer (mCRPC) in adults who have been treated with androgen receptor inhibitors and taxane-based chemotherapy

Approved in European Union as Pluvicto for:

• Treatment of adult patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitors and taxane-based chemotherapy

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is an approved treatment for adult patients with advanced prostate cancer that expresses the prostate-specific membrane antigen (PSMA).

This therapy is specifically indicated for patients who have already undergone treatment with androgen receptor pathway inhibitors and taxane-based chemotherapy, highlighting its role in later-stage cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Metastatic Castration-Resistant Prostate Cancer. Aschenbrenner, DS.[2022]

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is the first FDA-approved targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC), specifically for patients with high levels of prostate-specific membrane antigen (PSMA).

This treatment works by binding to PSMA, which is overexpressed in prostate cancer cells, allowing targeted radiation to damage DNA and induce cell death, making it a promising option in precision medicine for individualized cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Liu, X., Fang, GC., Lu, H., et al.[2023]

Lutetium Lu 177 vipivotide tetraxetan (PLUVICTO™) is a targeted radioligand therapy approved in the USA for treating metastatic castration-resistant prostate cancer (mCRPC) that expresses prostate-specific membrane antigen (PSMA), based on positive results from the phase 3 VISION trial.

This therapy specifically targets PSMA, which is overexpressed in prostate cancer cells, allowing for a more effective treatment option for patients who have already undergone other therapies like androgen receptor inhibition and taxane-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Keam, SJ.[2022]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

177Lu-vipivotide tetraxetan is a targeted radiopharmaceutical that effectively treats metastatic castration-resistant prostate cancer (mCRPC) by delivering beta-radiation directly to cancer cells, demonstrating safety and tolerability in clinical trials.

Approved by the FDA in March 2022 based on the VISION trial, this therapy is particularly beneficial for patients who have already undergone androgen receptor pathway inhibition and taxane-based chemotherapy, highlighting its role as a new treatment option in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. Shah, H., Ravi, P., Sonpavde, G., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.63

Patient characteristics and overall survival with lutetium (Lu ... The median OS from start of 177Lu-PSMA-617 therapy was 15.3 months (95% confidence interval [CI]: 14.6–16.3); a total of 137/643 (21.3%) ...

2. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158159-asco-gu-2025-patient-characteristics-and-overall-survival-with-lutetium-lu177-vipivotide-tetraxetan-177lu-psma-617-a-real-world-analysis-of-early-adopters.html

Patient characteristics and overall survival with lutetium ... The median overall survival from the start of ¹⁷⁷Lu-PSMA-617 therapy was 15.3 months (95% CI: 14.6–16.3), with 137 of 643 patients (21.3%) ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425002040

Lutetium Lu 177 Vipivotide Tetraxetan Efficacy and Toxicity ... 68.9% of the cohort observed PSA biomarker improvement of ≥10%, and 55.6% with ≥50% PSA reduction. Three patients (6.7%) achieved a complete ...

4. novartis.com novartis.com/news/media-releases/psmaddition-data-show-novartis-pluvictotm-delays-progression-end-stage-prostate-cancer

PSMAddition data show Novartis Pluvicto™ delays ... PluvictoTM plus standard of care (ARPI + ADT) significantly reduced risk of progression or death by 28% (HR 0.72) versus SoC alone, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9099330/

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval - PMC Lutetium Lu 177 vipivotide tetraxetan was more effective than cabazitaxel in achieving a PSA response (PSA reduction of ≥ 50% from baseline; primary endpoint) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36811416/

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer Lutetium Lu 177 vipivotide tetraxetan is a radioligand that strongly binds to PSMA, making it ideal for treating cancers of the prostate by targeted radiation.

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

Survival outcomes of patients (pts) with metastatic ... Survival outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177-PSMA-617 (Lu) based on ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-08714

Long-Term Safety of Lutetium (177Lu) Vipivotide ... The purpose of this post-marketing study is to further characterize the long-term outcome of known or potential risks of lutetium (177Lu) vipivotide ...