177Lu-PSMA-I&T for Prostate Cancer

Recruiting at 60 trial locations

Overseen By Darcy Denner

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Curium US LLC

Must be taking: ARAT therapy

Must not be taking: Radioligand therapy, Radium-223

Disqualifiers: Chemotherapy, ECOG PS ≥ 2, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: 36 weeks

439 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new radioactive drug against standard hormone therapy in men with advanced prostate cancer that doesn't respond to usual treatments. The drug targets and kills cancer cells using radiation. The drug being tested, 225Ac-PSMA-617, has shown promise in inducing complete responses in patients with metastatic castrate-resistant prostate cancer who were resistant to standard therapies.

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 participate if you are on certain treatments like radioligand therapy, radium-223, or investigational drugs within the last 4 weeks. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug 177Lu-PSMA-I&T, Abiraterone with Prednisone or Enzalutamide for prostate cancer?

Research shows that adding abiraterone or enzalutamide to standard hormone therapy improves outcomes for patients with metastatic prostate cancer. Additionally, enzalutamide can increase the levels of a protein called PSMA, which may make prostate cancer cells more responsive to treatments like 177Lu-PSMA-I&T. ^{1 2 3 4 5}

Is 177Lu-PSMA-I&T safe for humans?

In a small study, patients receiving 177Lu-PSMA radioligand therapy with added enzalutamide did not show any significant new safety concerns, suggesting it is generally safe in humans. ^{2 3 6 7 8}

How is the drug 177Lu-PSMA-I&T for prostate cancer different from other treatments?

The drug 177Lu-PSMA-I&T is unique because it combines a targeted radioligand therapy (a treatment that uses radioactive substances to target specific molecules on cancer cells) with either abiraterone and prednisone or enzalutamide, which are medications that block hormones fueling prostate cancer growth. This combination aims to enhance the effectiveness of the radioligand therapy, especially in patients who may not respond well to standard treatments. ^{3 4 7 9 10}

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to hormone therapy can join. They must have tried and progressed on treatments like abiraterone or enzalutamide, but not more than one type. A positive PSMA-PET scan is needed, and they should be effectively castrated with low testosterone levels. HIV or hepatitis B/C patients may qualify if well-managed. Participants need a life expectancy of at least 6 months and agree to use contraception.

Inclusion Criteria

My cancer has worsened, shown by rising PSA levels, growth of tumors, or new bone lesions.

Life expectancy of at least 6 months

My hepatitis B or C symptoms are under control.

Exclusion Criteria

My physical functioning is somewhat limited.

I have had chemotherapy for prostate cancer that did not respond to hormone therapy, with some exceptions.

Participants who have a pregnant partner or are capable of fathering a child and who are unwilling to take precautions to prevent potential harm to the fetus or prevent pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 177Lu-PSMA-I&T or hormone therapy. Those in the investigational group receive up to 6 treatments every 6 weeks.

36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and safety labs.

156 weeks

Pharmacokinetic and Radiation Dosimetry Sub-study

30 patients participate in a sub-study with SPECT imaging after each treatment cycle for dosimetry analysis.

36 weeks

Treatment Details

Interventions

• 177Lu-PSMA-I&T
• Abiraterone with Prednisone or Enzalutamide

Trial Overview This study compares the safety and effectiveness of a new treatment called 177Lu-PSMA-I&T against standard hormone therapies (abiraterone with prednisone or enzalutamide) in men whose prostate cancer has spread despite castration. It's an open-label trial where everyone knows which treatment they're getting, and it randomly assigns participants to either group.

Participant Groups

Group I: Investigational Drug Experimental Treatment 1 Intervention

177Lu-PSMA-I\&T

Group II: Standard Of Care Hormone Therapy Active Control 1 Intervention

Abiraterone with Prednisone or Enzalutamide

Who Is Running the Clinical Trial?

Curium US LLC

Lead Sponsor

Trials

6

Recruited

1,000+

Findings from Research

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a study of 26 metastatic castration-resistant prostate cancer patients treated with enzalutamide or abiraterone, changes in Prostate-Specific Membrane Antigen (PSMA) expression on PET/CT scans were strongly associated with treatment response, indicating that PSMA PET/CT can be a reliable tool for monitoring efficacy.

All patients who responded to treatment also showed a decrease in PSMA expression, while non-responders had stable or increased PSMA levels, suggesting that PSMA expression changes can effectively predict patient outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients. Plouznikoff, N., Artigas, C., Sideris, S., et al.[2021]

Enzalutamide treatment significantly increases PSMA expression in prostate cancer cell lines and tumors, which could make patients with low PSMA levels eligible for PSMA-directed radioligand therapy (RLT).

In a study involving human prostate cancer cell lines and a mouse model, enzalutamide treatment led to a notable increase in PSMA levels, as confirmed by PET/CT imaging, suggesting a potential strategy to enhance the effectiveness of RLT in metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. Staniszewska, M., Fragoso Costa, P., Eiber, M., et al.[2021]

In men with hormone-sensitive prostate cancer, androgen blockade treatment led to a significant reduction in PSMA PET imaging signals (SUVmax) by day 9, with a 30% median decrease and a 100% PSA response rate, indicating effective early treatment response.

Conversely, in men with castrate-resistant prostate cancer, androgen blockade resulted in a 45% increase in PSMA PET imaging signals by day 9, suggesting a different response pattern that may complicate treatment planning and interpretation of imaging results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial 68Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade. Emmett, L., Yin, C., Crumbaker, M., et al.[2021]

In a study of 133 patients with non-metastatic castration-resistant prostate cancer, abiraterone acetate (AA) plus prednisone showed comparable overall survival and cancer-specific survival to enzalutamide (Enz) over a median follow-up of 36 months.

However, patients treated with AA plus prednisone had a significantly higher risk of non-cancer-caused death compared to those treated with Enz, suggesting that while both treatments are effective, AA plus prednisone may pose additional safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. Tsujino, T., Tokushige, S., Komura, K., et al.[2023]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. [2021]

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

Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial 68Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade. [2021]

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

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Addition of Standard Enzalutamide Medication Shows Synergistic Effects on Response to [177Lu]Lu-PSMA-617 Radioligand Therapy in mCRPC Patients with Imminent Treatment Failure-Preliminary Evidence of Pilot Experience. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

New insights in the paradigm of upregulation of tumoral PSMA expression by androgen receptor blockade: Enzalutamide induces PSMA upregulation in castration-resistant prostate cancer even in patients having previously progressed on enzalutamide. [2021]

9. 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]

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

Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment. [2023]