177Lu-PSMA-617 for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Akshata Mathur

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Androgen deprivation therapy

Must not be taking: Radioligand therapy

Disqualifiers: CNS metastases, Congestive heart failure, 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

Compensation: Varies

Number of Visits: 19

Duration: Up to 36 weeks

51 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have any systemic anti-cancer therapy or investigational agents within 30 days before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that Lutetium Lu 177-PSMA-617 is effective in reducing prostate-specific antigen (PSA) levels and metastasis in patients with advanced prostate cancer, particularly those who have not responded to standard treatments. This treatment targets cancer cells specifically, which can improve patient outcomes and quality of life. ^{1 2 3 4 5}

Is 177Lu-PSMA-617 safe for humans?

177Lu-PSMA-617 has been studied for safety in patients with prostate cancer, and while it shows promise, the safety profile is still being evaluated. Some studies have focused on its use in combination with other treatments to improve outcomes. ^{1 2 5 6 7}

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 be more effective and have fewer side effects compared to traditional chemotherapy, as it minimizes damage to healthy tissues. ^{5 8 9 10 11}

What is the purpose of this trial?

This phase II trial tests how well 177Lu-PSMA-617 works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that remains despite treatment (resistant). Lutetium Lu 177 (177Lu), the radioactive (tracer) component being delivered by prostate-specific membrane antigen (PSMA)-617, has physical properties that make it ideal radionuclide (imaging tests that uses a small dose tracer) for treatment of metastatic castrate-resistant prostate cancer (mCRPC). 177Lu-PSMA-617 works by binding to prostate cancer cells and inducing damage to deoxyribonucleic acid (DNA) inside prostate cancer cells. Giving 177Lu-PSMA-617 may improve treatment outcomes for patients with mCRPC.

Research Team

Amir Iravani, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for patients with prostate cancer that has spread and is resistant to treatment. Participants must have a specific low level of PSMA expression, which will be determined by scans.

Inclusion Criteria

I understand and can follow all study requirements.

My PET/CT scan shows cancer that is PSMA positive without any PSMA negative spots.

White blood cell (WBC) count ≥ 2.5 x 10^9/L

Exclusion Criteria

Known hypersensitivity to the components of the study therapy or its analogs

I am not currently receiving any other cancer treatments like chemotherapy or immunotherapy.

I have had brain metastases, received treatment, and am now stable.

Timeline

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 30 minutes on specified days, with imaging and blood sample collection throughout the study

Up to 36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 12 weeks

Up to 2 years

Every 12 weeks (in-person)

Treatment Details

Interventions

• Lutetium Lu 177-PSMA-617

Trial Overview The study tests the effectiveness of an intensified dose of 177Lu-PSMA-617 in treating metastatic castrate-resistant prostate cancer (mCRPC). It involves various imaging techniques like bone scans, CTs, PET-CTs, SPECT, MRI, and biospecimen collection.

Participant Groups

Group I: Treatment (177Lu-PSMA-617) Experimental Treatment 8 Interventions

Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Society of Nuclear Medicine and Molecular Imaging (SNMMI) Mars Shot Research Fund

Collaborator

Trials

1

Recruited

50+

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

Findings from Research

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]

The ENZA-p trial is investigating the safety and efficacy of combining lutetium-177 (177 Lu)-PSMA-617 with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), aiming to improve prostate-specific antigen (PSA) progression-free survival (PFS) in high-risk patients.

This phase 2 trial will enroll 160 participants and assess various outcomes, including overall survival and quality of life, while also identifying potential biomarkers to personalize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). Emmett, L., Subramaniam, S., Joshua, AM., 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]

[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 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]

A 76-year-old man with advanced prostate cancer showed significant improvement after treatment with lutetium 177 PSMA-617, indicating its potential efficacy in patients resistant to standard therapies.

The treatment led to marked biochemical and imaging responses, as well as improvements in clinical status and pain relief, highlighting the therapeutic benefits of PSMA-targeted nuclear medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate Cancer. Parihar, AS., Hofman, MS., Iravani, A.[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]

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]

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]

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]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). [2022]

4. 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]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. [2023]

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

177Lu-Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate Cancer. [2023]

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

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

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

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]

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

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. [2022]