177Lu-PSMA-617 + SBRT for Prostate Cancer

Recruiting at 6 trial locations

Overseen By Michael Morris, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Adrenal inhibitors

Disqualifiers: Castration resistant prostate cancer, 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: Unknown

Duration: 8-12 weeks

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining 177Lu-PSMA-617, a treatment targeting prostate cancer cells, with Stereotactic Body Radiotherapy (SBRT) is safe and effective in stopping or slowing the spread of prostate cancer. It targets individuals with prostate cancer who have undergone surgery or radiation and currently have 1-5 detectable tumors. Participants should not have received recent prostate cancer treatments and need a specific scan confirming the cancer's presence. 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 innovative therapy.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that concurrent use of corticosteroids, adrenal hormone inhibitors, PC-SPES, finasteride, or dutasteride is not allowed. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that 177Lu-PSMA-617 is generally safe and has yielded promising results in earlier studies. In one study, patients who received this treatment alongside standard care maintained a good safety record, even those with advanced prostate cancer. Most side effects, such as fatigue and dry mouth, were manageable.

For the SBRT (stereotactic body radiation therapy) component, studies indicate it is a safe option with tolerable side effects. Long-term follow-ups suggest that while some patients experienced urinary issues, most returned to their normal state after treatment.

Overall, studies have found both 177Lu-PSMA-617 and SBRT to be well-tolerated, suggesting a reasonable safety profile for patients considering joining a trial with these treatments. ^{1 2 3 4 5}

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

Researchers are excited about 177Lu-PSMA-617 because it offers a new way to target prostate cancer that differs from standard treatments like hormone therapy and chemotherapy. This treatment uses a radioactive molecule, 177Lu, which is specifically designed to seek out and bind to PSMA, a protein found in abundance on prostate cancer cells. Once attached, it delivers radiation directly to the cancer cells, minimizing damage to surrounding healthy tissue. This targeted approach not only enhances precision but also has the potential to improve outcomes with fewer side effects compared to traditional therapies.

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

Research has shown that 177Lu-PSMA-617 effectively treats prostate cancer. Studies have found it can help patients with metastatic prostate cancer live longer and slow disease progression. One study revealed that 50.6% of patients experienced a significant drop in PSA levels, indicating reduced prostate cancer activity. Meanwhile, SBRT, a precise type of radiation therapy, has proven effective in controlling prostate cancer, with an 83.6% 5-year rate of preventing cancer progression. In this trial, participants will receive a combination of 177Lu-PSMA-617 and SBRT, which together show promise in delaying the spread of prostate cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Brandon Imber, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for men with prostate cancer who've had primary treatment at least 2 years ago, have a specific type of tumor detectable by PSMA scan, and haven't received recent prostate-cancer therapy. They must be healthy enough for radiation therapy, not have castration-resistant cancer or certain other health conditions, and agree to use contraception.

Inclusion Criteria

I can take care of myself and perform daily activities.

My liver function tests are within normal ranges.

My insurance covers SBRT treatment or I can pay for it myself.

Exclusion Criteria

I currently have an active infection.

I have not had any cancer except for skin cancer in the last 3 years.

Receipt of any other investigational agents or participation in a concurrent treatment protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 177Lu-PSMA-617 followed by stereotactic body radiotherapy (SBRT) to target tumor cells

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-617
• Stereotactic Body Radiotherapy (SBRT)

Trial Overview The study tests if combining a targeted radioactive drug called 177Lu-PSMA-617 with Stereotactic Body Radiotherapy (SBRT) is safe and effective in treating prostate cancer that has spread but is limited in number and location.

How Is the Trial Designed?

Group I: Stereotactic Body Radiotherapy and 177Lu-PSMA-617 Experimental Treatment 2 Interventions

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

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 phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of 177Lu-PSMA-617 to standard care significantly improved both imaging-based progression-free survival (8.7 months vs. 3.4 months) and overall survival (15.3 months vs. 11.3 months).

While 177Lu-PSMA-617 was associated with a higher incidence of grade 3 or above adverse events (52.7% vs. 38.0%), it did not negatively impact the patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. Sartor, O., de Bono, J., Chi, KN., et al.[2023]

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]

[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]

[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 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 phase 2 trial involving 200 men with metastatic castration-resistant prostate cancer, [177Lu]Lu-PSMA-617 showed a significantly higher prostate-specific antigen (PSA) response rate (66%) compared to cabazitaxel (37%), indicating its greater efficacy as a treatment option.

Patients receiving [177Lu]Lu-PSMA-617 experienced fewer severe adverse events (33%) compared to those on cabazitaxel (53%), suggesting a better safety profile for the radiolabeled therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Hofman, MS., Emmett, L., Sandhu, S., et al.[2023]

In a study of 75 patients with metastatic prostate cancer, 6 were excluded from Lutetium-177 [177Lu]-PSMA-617 treatment due to PSMA-negative/FDG-positive discordance, but 89 suitable targets for biology-guided radiotherapy (BgRT) were identified.

The research suggests that combining BgRT with Lutetium-177 [177Lu]-PSMA-617 is feasible for treating patients with discordant metastases, particularly highlighting that bone and lung metastases are the most suitable candidates for this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. Gaudreault, M., Chang, D., Hardcastle, N., et al.[2023]

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]

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]

Citations

1. 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.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39327018/

Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic ... This study aimed to evaluate the efficacy and safety profile of [ 177 Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial.

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

Lutetium-177–PSMA-617 for Metastatic Castration ... The PSMA-targeted radioligand 177Lu-PSMA-617 prolonged overall survival and delayed imaging-based progression when added to standard care in patients with PSMA- ...

5. 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 ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10071785/

Safety and Survival Outcomes of 177Lu-Prostate-Specific ... The VISION study investigated a β-emitter, 177Lu-PSMA-617, targeting PSMA-expressing cells and found prolonged overall survival and acceptable safety in heavily ...