Lu-177 Ludotadipep for Prostate Cancer

(LUCIDA Trial)

Recruiting at 3 trial locations

Overseen By Ronald Tutrone, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: FutureChem

Must be taking: GnRH therapy

Must not be taking: Anticoagulants, Herbal products

Disqualifiers: Impaired organ function, Brain metastasis, Thromboembolism, others

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

Compensation: Varies

Number of Visits: 7

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called [177Lu]Ludotadipep, a radiopharmaceutical therapy, for prostate cancer. The goal is to determine if this treatment is safe and effective, particularly for those whose cancer has worsened despite treatments like enzalutamide or abiraterone. It suits men whose prostate cancer progresses even after other hormonal therapies and who have a specific type of lesion visible in scans. Participants will assist researchers in finding the right dose and assessing if repeated treatments can effectively manage their cancer. This trial targets those who have tried other options but need a new solution. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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

The trial does not specify if you need to stop taking your current medications, but it does allow ongoing androgen deprivation therapy and requires stable doses of bisphosphonate therapy. You should discuss your specific medications with the trial team.

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

Studies have shown that [177Lu]Ludotadipep is generally safe for patients with prostate cancer. Research indicates that patients usually tolerate the treatment well, with some studies specifically examining doses up to 3.7 GBq. This dose is expected to be safe for repeated treatments, as planned in upcoming trials.

However, some known risks exist. Long-term follow-up has identified possible side effects such as myelosuppression, which decreases bone marrow activity and can lead to lower blood cell counts, and kidney problems. Reports also mention dry mouth and dry eyes. While these risks exist, trials are carefully monitoring them to ensure participants' safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

[177Lu]Ludotadipep is unique because it utilizes a radioactive compound, Lutetium-177, to specifically target and attack prostate cancer cells. This treatment stands out from traditional options like hormone therapy or chemotherapy because it offers a targeted approach, potentially reducing damage to healthy cells and minimizing side effects. Researchers are excited about [177Lu]Ludotadipep because it combines the precision of targeted therapy with the potent effects of radiotherapy, which could lead to improved outcomes for patients with prostate cancer.

What evidence suggests that [177Lu]Ludotadipep might be an effective treatment for prostate cancer?

Research has shown that [177Lu]Ludotadipep, the investigational treatment in this trial, may help treat prostate cancer. In a study with 30 patients, 66.7% experienced a drop in their PSA levels, indicating the treatment's effectiveness. PSA, or prostate-specific antigen, is a substance used to monitor prostate cancer progress. Early results suggest that [177Lu]Ludotadipep could be effective with fewer side effects, as it specifically targets cancer cells in the prostate. These findings offer hope for its potential in managing prostate cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Arif Hussain, MD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

Men aged 18+ with advanced prostate cancer that has resisted hormone therapy and progressed after treatments like enzalutamide or abiraterone. They must have PSMA positive lesions, be on stable doses of bisphosphonate if applicable, may have had taxane chemotherapy or not based on certain conditions, and should have an expected lifespan of at least 3 months for Phase 1 (6 months for Phase 2a). Participants need to use birth control during the study.

Inclusion Criteria

Patients who have partners of childbearing potential must use a method of birth control

Serum testosterone level < 50 ng/dL

Able and willing to provide signed informed consent and comply with protocol requirements

Exclusion Criteria

I have not had a blood clot in the past 3 months.

I have brain metastasis or active leptomeningeal disease.

I haven't had cancer treatment in the last 4 weeks, with some exceptions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Phase 1 Treatment

Participants receive a single dose of [177Lu]Ludotadipep to determine safety and tolerability

8 weeks

Continuous monitoring for adverse events

Phase 2a Treatment

Participants receive repeated doses of [177Lu]Ludotadipep every 8 weeks to evaluate safety and efficacy

up to 40 weeks

4 to 6 visits (in-person) every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks after each dose

2 visits (in-person) after each dose

Long-term Follow-up

Participants are monitored every 6 months for 2 years, with an option for long-term follow-up up to 10 years

2 to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• [177Lu]Ludotadipep

Trial Overview [177Lu]Ludotadipep is being tested in two phases. Phase 1 aims to find the safest dose by starting with a single injection of 3.7 GBq, possibly lowering it if needed. In Phase 2a, they'll test this dose's safety and effectiveness when given repeatedly based on results from earlier trials.

How Is the Trial Designed?

Group I: [177Lu]Ludotadipep 3.7 GBq Experimental Treatment 1 Intervention

If investigators observed one or no DLT in 6 patients at the 3.7 GBq dose level, the study can advance to the Phase 2a part of the trial after the safety review committee (SRC) review.

Who Is Running the Clinical Trial?

FutureChem

Lead Sponsor

Trials

6

Recruited

620+

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-na&#239;ve 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]

Lutetium-177 coupled with a ligand for Prostate Specific Membrane Antigen ([177Lu]Lu-PSMA) is an innovative treatment for patients with advanced prostate cancer who have limited options after hormonal therapy and chemotherapy, requiring specific eligibility criteria including good health and adequate targeting of metastases.

The treatment involves four to six intravenous doses administered six weeks apart, with mild side effects such as dry mouth, fatigue, and bone marrow depression, and is currently available in select hospitals in the Netherlands, with broader access expected following EMA registration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lutetium-177-PSMA in metastasized prostate carcinoma]. van Golen, LW., Vogel, W., Lam, MGEH.[2023]

In a study involving 30 patients with metastatic castration-resistant prostate cancer (mCRPC), [177Lu]Ludotadipep showed promising efficacy, with 66.7% of subjects experiencing a decrease in PSA levels after treatment, indicating a potential therapeutic benefit.

The treatment was associated with a manageable safety profile, as 58.6% of patients experienced treatment-emergent adverse events, but only 10.3% had serious adverse drug reactions, suggesting low toxicity for this targeted radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single Dose of Novel PSMA-Targeting Radiopharmaceutical Agent [177Lu]Ludotadipep for Patients with Metastatic Castration-Resistant Prostate Cancer: Phase I Clinical Trial. Shin, D., Ha, S., O, JH., et al.[2022]

Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) has become a promising treatment option for neuroendocrine tumors and prostate cancer, with Lutathera® and Pluvicto® being key approved therapies.

The review emphasizes the need for comprehensive safety data and optimized procedures for using 177Lu radiopharmaceuticals, aiming to improve the risk-benefit balance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. Ladrière, T., Faudemer, J., Levigoureux, E., et al.[2023]

Lutetium-177 (177Lu) radiopharmaceuticals are increasingly used for treating metastatic neuroendocrine tumors and prostate adenocarcinoma, highlighting their growing importance in targeted cancer therapies.

The paper emphasizes the need for patient-specific dosimetry to optimize treatment effectiveness and minimize radiation-induced side effects on normal tissues, providing guidance on dosimetry methods for various organs and tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands. Sjögreen Gleisner, K., Chouin, N., Gabina, PM., et al.[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]

Lutetium-177 coupled with a ligand for Prostate Specific Membrane Antigen ([177Lu]Lu-PSMA) is an innovative treatment for patients with advanced prostate cancer who have limited options after hormonal therapy and chemotherapy, requiring specific eligibility criteria including good health and adequate targeting of metastases.

The treatment involves four to six intravenous doses administered six weeks apart, with mild side effects such as dry mouth, fatigue, and bone marrow depression, and is currently available in select hospitals in the Netherlands, with broader access expected following EMA registration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lutetium-177-PSMA in metastasized prostate carcinoma]. van Golen, LW., Vogel, W., Lam, MGEH.[2023]

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]

Lutetium-177 labeled PSMA radioligand therapy ([177Lu]Lu-PSMA RLT) has shown effectiveness in reducing PSA levels, improving quality of life, and alleviating pain in metastatic castration-resistant prostate cancer (mCRPC) patients, although about 30% of patients do not respond to this treatment.

The reduction in PSA levels after [177Lu]Lu-PSMA RLT is a consistent predictor of prolonged survival, highlighting its importance as a prognostic factor, while other evaluated factors showed inconsistent results and require further investigation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors predicting biochemical response and survival benefits following radioligand therapy with [177Lu]Lu-PSMA in metastatic castrate-resistant prostate cancer: a review. Manafi-Farid, R., Harsini, S., Saidi, B., et al.[2022]

The study compared three PSMA-targeted PET imaging agents ([18F]DCFPyL, [68Ga]galdotadipep, and [68Ga]PSMA-11) to determine their effectiveness in visualizing prostate cancer, finding that [18F]DCFPyL and [68Ga]PSMA-11 had similar biodistribution and high tumor targeting efficiency.

Both [18F]DCFPyL and [68Ga]PSMA-11 are suitable for monitoring the therapeutic effects of the PSMA-targeted radiopharmaceutical [177Lu]ludotadipep in prostate cancer patients, as they demonstrated high uptake in tumor tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of PSMA target diagnostic PET tracers for therapeutic monitoring of [177Lu]ludotadipep of prostate cancer: Screening of PSMA target efficiency and biodistribution using [18F]DCFPyL and [68Ga]PSMA-11. Kim, MH., Lee, K., Oh, K., et al.[2023]

The LuTectomy trial is a phase 1/2 study assessing the safety and effectiveness of lutetium-177-radiolabelled PSMA-617 in men with high-risk localized prostate cancer, focusing on those with high PSMA expression.

This trial evaluates dosimetry, efficacy, and toxicity in patients undergoing radical prostatectomy and pelvic lymph node dissection, aiming to improve treatment outcomes for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trial Protocol for LuTectomy: A Single-arm Study of the Dosimetry, Safety, and Potential Benefit of 177Lu-PSMA-617 Prior to Prostatectomy. Dhiantravan, N., Violet, J., Eapen, R., et al.[2022]

The VISION trial demonstrated that Lutetium-177[177Lu]Lu-PSMA-617 significantly improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy, marking a breakthrough in treatment options.

Both the VISION and TheraP trials showed that [177Lu]Lu-PSMA-617 has a favorable safety profile, with common side effects including fatigue and nausea, suggesting it could be beneficial even for patients who have undergone extensive prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617: A Vision of the Future. Chandran, E., Figg, WD., Madan, R.[2022]

Citations

1. spandidos-publications.com spandidos-publications.com/10.3892/etm.2024.12514

Current clinical application of lutetium‑177 in solid tumors ... Prostate cancer and 177Lu-PSMA-617​​ The analysis showed that 177Lu-PSMA-617 therapy resulted in a combined PSA reduction rate of 68.00% [95% ...

2. urotoday.com urotoday.com/conference-highlights/2022-annual-meeting/aua-2022-prostate-cancer/137174-aua-2022-initial-experience-of-177lu-ludotadipep-treatment-in-patients-with-18f-psma-pet-ct-positive-mcrpc-preliminary-study.html

AUA 2022: Initial Experience of [177Lu] Ludotadipep ... To evaluate the treatment outcome, serum PSA levels were followed up in 1st, 2nd, 3rd, 4th, 6th, 8th, 12th weeks and [18F] PSMA PET CT was taken ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36551710/

A Single Dose of Novel PSMA-Targeting ... These data thus far suggest that [177Lu]Ludotadipep could be a promising RPT agent with low toxicity in mCRPC patients who have not been ...

4. withpower.com withpower.com/trial/phase-2-metastatic-castration-resistant-prostate-cancer-7-2022-6a030

Lu-177 Ludotadipep for Prostate Cancer (LUCIDA Trial) In a study with 30 patients, [177Lu]Ludotadipep showed promising results for prostate cancer, with 66.7% of patients experiencing a decrease in PSA levels, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05458544

Study Details | NCT05458544 | [Lu-177]Ludotadipep in ... The objective of the Phase 2a part of the trial is to evaluate safety and efficacy for repeated administration of the recommended [177Lu]Ludotadipep dose.

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

Safety and Survival Outcomes of 177Lu-Prostate-Specific ... 177 Lu-PSMA treatment was well tolerated in patients who had received prior 223 Ra. 223 Ra use before 177 Lu-PSMA is feasible and can be considered for future ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10831299/

Dosimetric Analysis of a Phase I Study of PSMA-Targeting ... [177Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05458544

Study Details | [Lu-177]Ludotadipep in Castration-resistant ... In the long-term survival follow-up, the long-term outcome of the known serious risk of myelosuppression, renal failure, xerostomia, xerophthalmia, and their ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2405456924001548

New Drugs for Targeted Radionuclide Therapy in ... Lutetium-177 is the radionuclide most commonly used for therapeutic purposes in prostate cancer TRT, mainly linked to small PSMA ligands ([177Lu]Lu-PSMA-617 or ...