Radioactive Drug Therapy for Prostate Cancer

Recruiting at 14 trial locations

Overseen By Ana Aparicio

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: LHRH agonists/antagonists

Must not be taking: Long-acting somatostatin

Disqualifiers: Uncontrolled hypertension, Stroke, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a radioactive drug, lutetium Lu 177 dotatate, treats prostate cancer that has spread and exhibits neuroendocrine traits. These traits involve cells behaving like both hormone-producing and nerve cells, potentially making the cancer more aggressive. The drug targets specific proteins on these cancer cells and emits radiation to potentially kill them. This trial suits those with prostate cancer that has spread and shows neuroendocrine characteristics, such as small or large cells with certain markers or specific genetic features. As a Phase 2 trial, researchers focus on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using long-acting somatostatin analogs (like long-acting octreotide) 4 weeks before starting the treatment and during the trial. Short-acting somatostatin analogs must be stopped 24 hours before starting the treatment and during the trial, unless you have a history of carcinoid syndrome and need them for symptom control.

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

Research has shown that lutetium Lu 177 dotatate is generally well-tolerated for treating certain cancers. However, some patients have experienced serious but rare complications, such as blood disorders like acute myeloid leukemia, a type of blood cancer.

While most patients do not encounter these severe problems, awareness of potential risks is important. Overall, the treatment has shown promise in shrinking tumors, particularly in cancers where cells have characteristics of both hormone-producing and nerve cells.

For those considering joining a trial, understanding both the potential benefits and risks is crucial. Discuss with a doctor what these findings mean personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike standard treatments for prostate cancer, such as hormone therapy or chemotherapy, lutetium Lu 177 dotatate offers a novel approach by using targeted radioactive therapy. This treatment is unique because it combines a radioactive component, lutetium-177, with dotatate, which specifically binds to cancer cells. This targeted mechanism allows the radioactive particles to deliver precise doses of radiation directly to the tumor, potentially reducing harm to healthy tissues. Researchers are excited about this treatment as it may offer a more effective and potentially less toxic option for patients with advanced prostate cancer.

What evidence suggests that Lutetium Lu 177 dotatate might be an effective treatment for metastatic prostate cancer with neuroendocrine differentiation?

Research has shown that Lutetium Lu 177 dotatate, the treatment under study in this trial, can help treat certain cancers. In some studies, 68.9% of patients experienced at least a 10% improvement in their PSA levels, a marker used to track prostate cancer. Additionally, 55.6% of patients saw a reduction of 50% or more in their PSA levels. This treatment targets a specific protein on certain tumor cells, releasing radiation that may destroy these cells. It has effectively shrunk tumors, particularly those with neuroendocrine features, suggesting it could be a promising option for prostate cancer that has spread and involves these specialized cell types. ^{2 3 4 5 6}

Who Is on the Research Team?

John M. Floberg

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with metastatic prostate cancer that has neuroendocrine cells. Participants must not be using other cancer treatments, should have good organ function and performance status, and agree to use contraception. Those with controlled HIV or hepatitis, treated brain metastases, or a second malignancy not affecting the study can join.

Inclusion Criteria

I have another cancer that won't affect this treatment's safety or results.

My heart condition does not severely limit my daily activities.

I am HIV-positive, on treatment, and my viral load is undetectable.

Exclusion Criteria

Patients with uncontrolled intercurrent illness

I have not used long-acting somatostatin analogs in the last 4 weeks or short-acting ones in the last 24 hours, unless to control carcinoid syndrome.

Your high blood pressure is not well controlled, based on specific blood pressure numbers at the screening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive lutetium Lu 177 dotatate IV over 30 minutes. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

24 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs at 6 weeks after the last dose and then every 3 months for 2 years.

2 years

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177 Dotatate

Trial Overview The trial tests Lutetium Lu 177 dotatate's effectiveness in shrinking tumors in patients with advanced prostate cancer having neuroendocrine differentiation. It involves collecting biospecimens and imaging through CT and PET scans to observe treatment outcomes.

How Is the Trial Designed?

Group I: Treatment (lutetium Lu 177 dotatate) Experimental Treatment 5 Interventions

Patients receive lutetium Lu 177 dotatate IV over 30 minutes. Cycles repeat Q6W for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive gallium Ga 68-dotatate IV during screening then undergo PET/CT scan at baseline and collection of blood throughout the trial.

Lutetium Lu 177 Dotatate is already approved in European Union, United States for the following indications:

Approved in European Union as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Approved in United States as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) is emerging as a promising treatment for castration-resistant metastatic prostate cancer, utilizing the targeted delivery of the radionuclide Lutetium-177 to cancer cells expressing the prostate-specific membrane antigen.

There is currently no prospective randomized data on Lu-177-PSMA-RLT, which raises questions about its reimbursement by health insurance in Germany, highlighting the need for clarity on its integration into treatment plans for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein]. Ahmadzadehfar, H., Albers, P., Bockisch, A., et al.[2019]

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 of 79 patients with progressive neuroendocrine tumors treated with Lu-DOTATATE, 13% showed a partial response and 64% had stable disease, with a median time to progression of 28 months overall.

The treatment was found to be safe, with only a few patients experiencing mild toxicity, including grade 1 haematotoxicity and nephrotoxicity, supporting its use as an effective option for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Pencharz, D., Walker, M., Yalchin, M., et al.[2019]

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]

Lutetium-177 dotatate (Lutathera®) is an effective outpatient treatment for neuroendocrine tumors, administered in four cycles of 7.4 GBq each, with minimal radiation exposure to staff and surrounding areas when proper safety protocols are followed.

The treatment can be safely conducted in standard hospital procedural rooms without the need for extra shielding, provided that precautions are taken to manage radiation exposure and contamination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Safety Observations Associated with 177Lu Dotatate Patients. Nelson, KL., Sheetz, MA.[2020]

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]

In a study involving 49 men with metastatic castration-resistant prostate cancer, fractionated doses of Lutetium-177-labeled anti-PSMA monoclonal antibody J591 (177 Lu-J591) allowed for higher cumulative radiation doses, leading to significant decreases in prostate-specific antigen (PSA) levels and improved survival rates.

The highest dose of 45 mCi/m2 resulted in notable toxicity, including reversible grade 4 neutropenia in 35.3% of patients, but also showed promising outcomes with 87.5% of patients experiencing any PSA decrease and a median survival of 42.3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of fractionated dose lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (177 Lu-J591) for metastatic castration-resistant prostate cancer. Tagawa, ST., Vallabhajosula, S., Christos, PJ., et al.[2020]

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]

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]

Hyperfractionation of lutetium-177 (177 Lu)-J591 for metastatic castration-resistant prostate cancer did not show additional benefits compared to single or two-dose fractionation regimens, indicating that more frequent dosing may not enhance treatment efficacy.

In a small study of six patients, 33% experienced significant declines in prostate-specific antigen (PSA) levels, but there were also notable instances of severe side effects like grade 4 neutropenia and thrombocytopenia, highlighting the need for careful monitoring and further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperfractionated Dosing of Lutetium-177-Labeled Antiprostate-Specific Membrane Antigen Monoclonal Antibody J591 (177 Lu-J591) for Metastatic Castration-Resistant Prostate Cancer. Niaz, MJ., Batra, JS., Walsh, RD., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05691465

Study Details | NCT05691465 | Testing the Safety and ... Treatment with Lutetium Lu 177 dotatate may shrink the tumor in a way that can be measured in patients with metastatic prostate cancer with neuroendocrine ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425002040

Lutetium Lu 177 Vipivotide Tetraxetan Efficacy and Toxicity ... 68.9% of the cohort observed PSA biomarker improvement of ≥10%, and 55.6% with ≥50% PSA reduction. Three patients (6.7%) achieved a complete ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10752594/

Case report: 177Lu DOTA-TATE: a new scheme for the ... 177Lu-DOTA-TATE demonstrates favorable efficacy in treating neuroendocrine tumors, but its current application primarily focuses on gastrointestinal ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/lutetium-lu-177-dotatate?pn=1

Clinical Trials Using Lutetium Lu 177 Dotatate - NCI Testing the Safety and Effectiveness of Radiation-based Treatment (Lutetium Lu 177 Dotatate) for Metastatic Prostate Cancer that has Neuroendocrine Cells.

5. aetna.com aetna.com/cpb/medical/data/900_999/0929.html

Lutetium Lu 177 Dotatate (Lutathera) and ... It is widely considered to be an effective treatment for well- or moderately differentiated neoplasms, which express high levels of SSTR that can be selectively ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10145759/

Safety and Therapeutic Optimization of Lutetium-177 Based ... One serious but infrequent complication of [¹⁷⁷Lu]Lu-DOTATATE therapy is the occurrence of myeloid neoplasms including acute myeloid leukemia (AML) and ...