Lu-177 Ludotadipep for Prostate Cancer

(LUCIDA Trial)

Recruiting at 3 trial locations

Overseen By Jeffry Chen, MSc

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial tests the safety and effectiveness of a radioactive drug called [177Lu]Ludotadipep. The drug works by delivering radiation directly to certain cells to treat the condition. Lutetium-177 (177Lu) has been widely used in targeted therapy, particularly in peptide receptor radionuclide therapy (PRRT) for treating neuroendocrine tumors.

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.

What data supports the effectiveness of the drug Lu-177 Ludotadipep for prostate cancer?

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, which is a marker for prostate cancer activity, and 37.5% showing a significant reduction of 50% or more. This suggests that the drug could be effective for patients who have not responded to other treatments. ^{1 2 3 4 5}

Is Lu-177 Ludotadipep safe for use in humans?

While specific safety data for Lu-177 Ludotadipep is not available, similar treatments like [177Lu]Lu-PSMA-617 have shown a good safety profile in clinical trials for prostate cancer. Common side effects include fatigue, nausea, dry mouth, and mild bone marrow suppression, but these treatments are generally considered safe even for patients who have undergone extensive prior treatments. ^{2 6 7 8 9}

What makes the drug Lu-177 Ludotadipep unique for treating prostate cancer?

Lu-177 Ludotadipep is a novel treatment that targets prostate-specific membrane antigen (PSMA) in prostate cancer cells, delivering radiation directly to the cancer and surrounding areas. This approach is similar to other PSMA-targeted therapies but may offer a new option for patients with limited treatment choices. ^{2 10 11 12 13}

Research Team

Arif Hussain, MD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• [177Lu]Ludotadipep (Radiopharmaceutical)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

[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 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 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]

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]

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]

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]

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 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]

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]

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]

References

1. Switzerland 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. [2022]

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-na&#239;ve 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

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

5. Germany 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. [2022]

6. Netherlands 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. [2022]

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

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. [2023]

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

Lutetium-177-PSMA-617: A Vision of the Future. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands. [2022]

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

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. [2023]

11. United States 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. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

[Lutetium-177-PSMA in metastasized prostate carcinoma]. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

[Lutetium-177-PSMA in metastasized prostate carcinoma]. [2023]