Lu-PSMA-617 for Liver Cancer

Overseen By Melissa Lumish, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Melissa Lumish

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Brain metastases, Uncontrolled illness, 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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

10 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or have received investigational therapy recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Lu-PSMA-617 for liver cancer?

Lu-PSMA-617 has shown success in treating liver metastases (spread of cancer to the liver) in prostate cancer patients, with significant reduction in tumor size and activity. This suggests potential effectiveness for liver cancer, although direct evidence for primary liver cancer is not available. ^{1 2 3 4 5}

Is Lu-PSMA-617 safe for use in humans?

Lu-PSMA-617 has been shown to be safe and well-tolerated in clinical trials for prostate cancer, with common side effects including dry mouth, fatigue, nausea, and diarrhea. Serious side effects were rare and manageable, and no significant changes in vital signs or blood tests were noted. ^{3 5 6 7 8}

How is the drug Lu-PSMA-617 unique for treating liver cancer?

Lu-PSMA-617 is unique because it is a targeted radioligand therapy that uses a radioactive substance to specifically target and bind to prostate-specific membrane antigen (PSMA) on cancer cells, which is not a standard approach for liver cancer. This method has shown success in shrinking liver metastases in prostate cancer, suggesting potential for liver cancer treatment. ^{1 3 5 6 9}

What is the purpose of this trial?

The purpose of this study is to look at the effects (good and bad) of a drug called 177Lu-PSMA-617 (also known as the study drug) when given to participants who have prostate specific membrane antigen (PSMA) positive liver cancer.

Research Team

Melissa Lumish, MD

Principal Investigator

Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center

Eligibility Criteria

This trial is for individuals with liver cancer that tests positive for a protein called PSMA. Specific details about who can join or reasons why someone might not be eligible are not provided in the information given.

Inclusion Criteria

I have had one treatment for my liver cancer that cannot be surgically removed.

My blood counts and kidney function are within normal ranges.

Participants must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

I have had Y90 treatment for liver cancer.

I had major surgery less than 3 months ago and haven't fully recovered.

I do not have untreated brain metastases or carcinomatous meningitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 177Lu-PSMA-617 intravenously every 6 weeks

6 weeks

1 visit (in-person) every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

52 weeks

Treatment Details

Interventions

• Lu-PSMA-617

Trial Overview The study is examining the effects of a drug named 177Lu-PSMA-617 on patients with PSMA-positive liver cancer to determine its safety and effectiveness.

Participant Groups

Group I: Lu-PSMA-617 Experimental Treatment 1 Intervention

Participants will receive 177Lu-PSMA-617 7.4 GBq (200 mCi) once every 6 weeks. 177Lu-PSMA-617 is a radiopharmaceutical which will be administered intravenously (IV).

Who Is Running the Clinical Trial?

Melissa Lumish

Lead Sponsor

Trials

1

Recruited

10+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Findings from Research

In a study of seven patients with progressive prostate cancer, (177)Lu-PSMA-617 therapy was found to be safe, with the highest radiation doses absorbed by the parotid glands (1.17 mGy/MBq) and kidneys (0.88 mGy/MBq), while the bone marrow received a significantly lower dose (0.03 mGy/MBq).

The findings suggest that the parotid glands are the dose-limiting organs in this therapy, indicating that individual patient dosimetry is essential due to substantial variations in radiation absorption among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. Kabasakal, L., AbuQbeitah, M., Aygün, A., et al.[2021]

[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]

In a study involving 64 patients with metastatic castration-resistant prostate cancer, 177Lu-PSMA-617 was found to be safe and well-tolerated, with manageable side effects such as dry mouth, fatigue, and nausea occurring in a significant number of patients.

The treatment did not lead to serious adverse events directly related to the drug, and there were no significant changes in vital signs or kidney function, suggesting a favorable safety profile for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). Calais, J., Czernin, J., Thin, P., et al.[2023]

In a study of 24 patients with hormone and/or chemorefractory metastatic prostate cancer, 79.1% experienced a decline in PSA levels after the first cycle of Lu-PSMA therapy, indicating a strong efficacy of this treatment.

Lu-PSMA therapy demonstrated a low toxicity profile, with only two cases of grade 3 anemia reported and no significant hemato- or nephrotoxicity, confirming its safety for patients with advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Ahmadzadehfar, H., Eppard, E., Kürpig, S., et al.[2022]

References

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

Successful Treatment of Hepatic Metastases of Hormone Refractory Prostate Cancer Using Radioligand Therapy With 177Lu-PSMA-617. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. [2021]

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [177Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis. [2023]

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

First Experience With 177Lu-PSMA-617 Therapy for Advanced Prostate Cancer in the Netherlands. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Prospects of medium specific activity (177) Lu in targeted therapy of prostate cancer using (177) Lu-labeled PSMA inhibitor. [2021]

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

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). [2023]

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

Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. [2022]

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

Pretherapeutic 68Ga-PSMA-617 PET May Indicate the Dosimetry of 177Lu-PSMA-617 and 177Lu-EB-PSMA-617 in Main Organs and Tumor Lesions. [2021]