177Lu-PSMA-617 for Prostate Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Weill Medical College of Cornell University

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

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer.

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.

What data supports the effectiveness of the treatment 177Lu-PSMA-617 for prostate cancer?

The treatment 177Lu-PSMA-617, also known as Pluvicto, has been shown in numerous clinical trials to effectively target and kill prostate cancer cells while sparing healthy tissue. It has been approved by the FDA for patients with advanced prostate cancer, and studies have demonstrated its ability to reduce prostate-specific antigen (PSA) levels and metastasis in patients who have not responded to other treatments. ^{1 2 3 4 5}

Is 177Lu-PSMA-617 safe for humans?

177Lu-PSMA-617 has been shown to have low toxicity in clinical trials for prostate cancer, with common side effects including mild dry mouth and nausea. Serious side effects like low blood platelet counts and anemia occurred in a small percentage of patients, but no unexpected adverse events were reported. ^{1 2 4 5 6}

What makes the drug 177Lu-PSMA-617 unique for prostate cancer treatment?

177Lu-PSMA-617 is unique because it is a radiopharmaceutical that specifically targets prostate-specific membrane antigen (PSMA) on prostate cancer cells, delivering beta-minus radiation directly to the cancer cells. This targeted approach can lead to better outcomes for patients with metastatic castration-resistant prostate cancer, especially those who have not responded well to other treatments. ^{1 7 8 9 10}

Research Team

Scott Tagawa, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

[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]

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]

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. [2023]

4. England 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). [2021]

5. England 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. [2021]

6. United States 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. [2022]

7. United States 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. [2020]

9. Germany 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical translation of (177)Lu-labeled PSMA-617: Initial experience in prostate cancer patients. [2021]