Radioactive Drug Therapy for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+13 other locations

Overseen by John M. Floberg

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial studies how well lutetium Lu 177 dotatate works in treating patients with a specific type of prostate cancer that has spread. The drug targets cancer cells and releases radiation to kill them. Lutetium-177 (Lu-177) PSMA therapy is a targeted treatment for advanced prostate cancer that has shown promising results.

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.

What data supports the effectiveness of the drug Lutetium Lu 177 Dotatate, Lutathera for prostate cancer?

Research on similar treatments, like Lutetium-177-PSMA-617, shows that this type of radioactive drug can target prostate cancer cells effectively, especially in advanced cases where other treatments have failed. This suggests that Lutetium Lu 177 Dotatate, Lutathera might also be effective in treating prostate cancer. ^{1 2 3 4 5}

Is Lutetium-177 based therapy safe for humans?

Lutetium-177 based therapies, like Lutathera and 177Lu-PSMA-617, have been used safely in treating certain cancers, with precautions to manage radiation exposure. These treatments are generally safe when proper procedures are followed, and they can be administered in hospital settings without additional shielding. ^{1 4 6 7 8}

How is the drug Lutetium Lu 177 Dotatate unique for treating prostate cancer?

Lutetium Lu 177 Dotatate is unique because it uses a radioactive substance to specifically target and deliver radiation to prostate cancer cells that express a protein called PSMA, which is not a common approach in standard treatments. This targeted radioligand therapy is administered intravenously and is particularly used for advanced prostate cancer that has not responded to other treatments. ^{1 5 9 10 11}

Research Team

John M. Floberg

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Lutetium Lu 177 Dotatate (Radioactive Drug)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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 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]

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]

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 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]

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]

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]

References

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

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

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

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. [2021]

4. United States 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. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

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

Radiation Safety Observations Associated with 177Lu Dotatate Patients. [2020]

8. 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]

9. Germany 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]. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]