177Lu-PSMA-617 for Prostate Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Weill Medical College of Cornell University

Must be taking: LHRH/GnRH analogues

Disqualifiers: Brain metastases, Other malignancy, others

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

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

Compensation: Varies

Number of Visits: 9

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called 177Lu-PSMA-617 (also known as Pluvicto or Lutetium Lu 177-PSMA-617) to determine the highest safe dose for treating advanced prostate cancer. The focus is on patients whose cancer has progressed despite treatments like hormonal therapies or chemotherapy. Participants should have prostate cancer that has spread and shown signs of worsening, such as increasing PSA levels or new bone lesions. The study aims to find the best dose that balances effectiveness with manageable side effects. 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 this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue taking androgen deprivation therapy if you haven't had an orchiectomy. You can also continue bisphosphonates or denosumab if you started them at least 4 weeks before the trial, but you cannot start these medications during the trial's assessment period.

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

Research has shown that 177Lu-PSMA-617 is generally well-tolerated by patients. This prostate cancer treatment usually causes manageable side effects. For instance, one study found that patients experienced less severe side effects compared to other treatments.

Another study examined the long-term safety of 177Lu-PSMA-617. It found that while some patients did experience side effects, they were usually not severe. The most common issues were minor, such as fatigue or dry mouth.

Overall, 177Lu-PSMA-617 appears safe for patients, with side effects that are often mild and manageable. This makes it a potential option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 177Lu-PSMA-617 for prostate cancer because it works differently from traditional treatments like hormone therapy, chemotherapy, or surgery. Unlike these options, which often target the whole body, 177Lu-PSMA-617 is a targeted radioligand therapy that specifically seeks out and binds to the prostate-specific membrane antigen (PSMA) on cancer cells. This precision allows it to deliver radiation directly to the cancer cells, potentially minimizing damage to healthy tissue and leading to fewer side effects. Additionally, its new mechanism of action offers hope for patients who have not responded well to existing treatments.

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

Research has shown that 177Lu-PSMA-617, which participants in this trial will receive, holds promise for treating advanced prostate cancer. Studies have found that combining this treatment with standard care can significantly extend the time patients live without their cancer worsening—from 3.4 months to 8.7 months. In real-world settings, more than half of the patients experienced a significant drop in PSA levels, a marker used to track prostate cancer. Additionally, the average overall survival for patients improved by about 4 months compared to other treatments. This drug targets PSMA, a protein abundantly found on prostate cancer cells, delivering radiation directly to them and helping to kill the cancer cells. ^{1 6 7 8 9}

Who Is on the Research Team?

Scott Tagawa, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced prostate cancer that's spreading and getting worse despite low testosterone levels and previous treatments like enzalutamide or taxane chemotherapy. Participants must have good organ function, no brain metastases, not be on certain bone medications recently, and agree to use birth control if they can have children.

Inclusion Criteria

My prostate cancer is worsening, shown by rising PSA levels, new bone lesions, or growth in scans.

I can take care of myself and perform daily activities.

I have been treated with specific prostate cancer drugs or have been deemed ineligible for or refused taxane chemotherapy.

Exclusion Criteria

I do not have serious heart, lung, brain, kidney, liver, or blood diseases that could affect my participation.

I received radiation for prostate cancer less than 4 weeks ago.

I haven't used any experimental drugs or devices in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive 177Lu-PSMA-617 intravenous doses, 2 weeks apart, with a total of 8 visits over 12 weeks

12 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including survival assessment until death

12 weeks

Follow-up evaluations

Long-term Follow-up

Participants are followed for overall survival and progression-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-617
• 68Ga-PSMA-HBED-CC

Trial Overview The study is testing different doses of a drug called 177Lu-PSMA-617 to find the highest dose that doesn't cause severe side effects in men with progressive metastatic CRPC (a type of prostate cancer). The drug targets cancer cells using a radioactive substance linked to a molecule that binds to PSMA receptors on tumors.

How Is the Trial Designed?

Group I: All subjects Experimental Treatment 2 Interventions

1. 177Lu-PSMA-617 \[50mCi (1.85GBq) - 300mCi (11.1GBq)\] intravenous X2 doses, 2 weeks apart (Visit 1 and 2) 2. 68Ga-PSMA-HBED-CC \[5 ±2mCi or 185 ±74MBq\] intravenous during screening and at 12 weeks with standard imaging

177Lu-PSMA-617 is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Approved in European Union as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

[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]

[177Lu]Lu-PSMA-617 (PluvictoTM) is an FDA-approved treatment for prostate cancer specifically for patients with PSMA-positive metastatic castration-resistant prostate cancer who have already undergone other therapies.

This treatment uses a targeted radioligand therapy that delivers radiation directly to tumor cells, effectively killing them while minimizing damage to healthy tissue, as shown in multiple clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Hennrich, U., Eder, M.[2022]

In a phase 2 trial involving 30 men with metastatic castration-resistant prostate cancer, 57% achieved a significant PSA decline of 50% or more after treatment with Lutetium-177 [177Lu]-PSMA-617, indicating its efficacy in this patient population.

The treatment was associated with low toxicity, with the most common side effects being mild dry mouth and transient nausea, and it also led to clinically meaningful improvements in pain and quality of life for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Hofman, MS., Violet, J., Hicks, RJ., et al.[2021]

The UpFrontPSMA trial is evaluating the effectiveness and safety of combining lutetium-177 (177 Lu)-PSMA-617 with docetaxel in 140 men with newly diagnosed metastatic hormone-naïve prostate cancer, aiming to determine the proportion of patients achieving undetectable PSA levels after 12 months.

This study is significant as it compares the experimental treatment to standard docetaxel therapy while all patients receive continuous androgen deprivation therapy, potentially providing insights into improved treatment strategies for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UpFrontPSMA: a randomized phase 2 study of sequential 177 Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol). Dhiantravan, N., Emmett, L., Joshua, AM., et al.[2021]

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]

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 study involving 40 chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), Lutetium-177 PSMA-617 showed a best prostate-specific antigen response rate of 60%, compared to 40% for docetaxel, demonstrating its efficacy as a treatment option.

177Lu-PSMA-617 was associated with fewer severe adverse events and significantly improved quality of life compared to docetaxel, suggesting it may be a safer alternative that could be used earlier in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. Satapathy, S., Mittal, BR., Sood, A., et al.[2022]

Treatment with lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA) significantly reduces prostate-specific antigen (PSA) levels in patients with advanced metastatic prostate cancer, especially after the first treatment cycle.

The therapy shows a beneficial effect on reducing lymph node metastasis, while also indicating potential negative impacts on visceral metastasis, highlighting its efficacy in managing certain aspects of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. Rathore, R., Rangrej, SB., Kieme, I., et al.[2023]

A reliable multidose formulation of [177Lu]Lu-PSMA-617 was developed for treating metastatic castrate-resistant prostate carcinoma (mCRPC), achieving a high radiochemical yield of 97.30% and purity of 98.24%, making it suitable for routine hospital use.

Preclinical studies showed that [177Lu]Lu-PSMA-617 specifically binds to prostate cancer cells and demonstrates significant localization in tumor regions, indicating its potential therapeutic efficacy in mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Multidose Preparation of a Ready-to-Use 177Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy. Chakraborty, A., Mitra, A., Tawate, M., 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]

Citations

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

Lutetium-177–PSMA-617 for Metastatic Castration ... Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months ...

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.97

Real world outcomes of 177 Lu-PSMA-617 ... The cohort completed a median number of 4 cycles of 177Lu-PSMA-617; 35.7% completed six cycles. The overall cohort had a 12-month survival of ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251559

Overall survival of prostate cancer patients treated with Lu-177 ... Median overall survival was found to be approximately 4 months higher than OS reported in VISION trial and equal to that in TheraP trial.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1558767325000989

Safety and Efficacy of Lutetium-177 PSMA Therapy for ... [177Lu]Lu-PSMA-617 is a radioactive drug that binds to PSMA and delivers radiation directly to prostate cancer cells. This can kill the cancer cells while ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39299783/

Initial Experience with [ 177 Lu]Lu-PSMA-617 After ... Patients who underwent [177Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate ...

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

Outcomes of [177Lu] Lu-PSMA-617 Re-Treatment in ... Introduction: Radioligand therapy (RLT) with [177Lu] Lu-PSMA-617 has shown significant benefits in metastatic castration-resistant prostate ...