Radioligand + Radiation Therapy for Prostate Cancer

Recruiting in Palo Alto (17 mi)

Overseen by David M. Schuster, MD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Emory University

Disqualifiers: Inflammatory bowel disease, Metastasis, Myelosuppression, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety, side effects and best dose of radioligand therapy (lutetium Lu 177 PSMA-10.1 \[177Lu-rhPSMA-10.1\]) after prostate specific membrane antigen (PSMA) positron emission tomography (PET)-guided external beam radiotherapy in treating post-prostatectomy patients with prostate cancer that has come back after a period of improvement (recurrent). In this study, radioligand therapy is a radioactive drug called 177Lu-rhPSMA-10.1. It works by binding to PSMA-expressing prostate tumor cells and delivering the radioactive portion of the drug directly to the tumor cells while not harming normal cells. Radiation therapy such as external beam radiotherapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radioligand therapy with PSMA PET-guided external beam radiotherapy may kill more tumor cells in post-prostatectomy patients with biochemically recurrent prostate cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Radioligand + Radiation Therapy for Prostate Cancer?

Research shows that Lutetium-177 (Lu-177) radioligand therapy, which targets prostate-specific membrane antigen (PSMA), is promising for treating metastatic castration-resistant prostate cancer. Studies indicate it can reduce prostate-specific antigen (PSA) levels and metastasis, suggesting it may be effective in managing advanced prostate cancer.

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Is the combination of radioligand and radiation therapy generally safe for humans?

Studies on Lutetium-177 PSMA radioligand therapy, used for prostate cancer, suggest it is generally safe, with some potential kidney-related concerns due to how the body processes the treatment. However, it has been used safely in patients with normal kidney function and even in those with a single functioning kidney.

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How is the drug Lutetium Lu 177 PSMA-10.1 different from other treatments for prostate cancer?

Lutetium Lu 177 PSMA-10.1 is a new type of radioligand therapy that targets a specific protein on prostate cancer cells, potentially offering better treatment outcomes for patients with advanced prostate cancer that has not responded to other therapies. It is designed to improve upon existing treatments by optimizing how the drug behaves in the body, which may lead to more effective tumor responses.

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Eligibility Criteria

Men over 18 with prostate cancer that has returned after surgery, who have detectable PSA levels and only show signs of cancer in the pelvic area on PSMA PET/CT scans. They should be relatively fit (ECOG status 0-2) and not have had prior radiotherapy or conditions like inflammatory bowel disease, severe kidney issues, high-risk urinary retention, significant liver damage, low blood counts, or serious acute illnesses.

Inclusion Criteria

I had surgery for prostate cancer and my PSA levels are now detectable.

I can take care of myself and am up and about more than half of the day.

I am over 18 years old.

Exclusion Criteria

Platelet count less than 75 x 10^9 /L

Liver enzymes > 5-fold ULN

Total white cell count less than 2.5 x 10^9 /L

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation

Participants undergo external beam radiation therapy (EBRT) guided by PSMA PET

4-6 weeks

Multiple visits (in-person)

Radioligand Therapy

Participants receive 177Lu-rhPSMA-10.1 intravenously

6 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

1 visit (in-person)

Participant Groups

This phase I trial is testing a new radioactive drug called lutetium Lu 177 PSMA-10.1 after external beam radiation therapy guided by PSMA PET scans. The goal is to find the safest dose that can effectively target tumor cells without harming normal ones in patients whose prostate cancer has come back post-surgery.

Group I: Treatment (EBRT, 177Lu-rhPSMA-10.1) Experimental Treatment 7 Interventions

Patients undergo EBRT followed by 177Lu-rhPSMA-10.1 IV on study. Patients also receive rhPSMA-7.3 IV with PET/CT at screening and undergo SPECT-CT and collection of blood samples on study.

Lutetium Lu 177 PSMA-10.1 is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Pluvicto for:

• PSMA-positive metastatic castration-resistant prostate cancer

🇪🇺 Approved in European Union as Pluvicto for:

• PSMA-positive metastatic castration-resistant prostate cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Emory University Hospital/Winship Cancer Institute Atlanta, GA

Who Is Running the Clinical Trial?

Emory University Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

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

177 Lu-rhPSMA-10.1 Induces Tumor Response in a Patient With mCRPC After PSMA-Directed Radioligand Therapy With 177 Lu-PSMA-I&T. [2023] 177 Lu-rhPSMA-10.1 is a novel PSMA-targeting radiopharmaceutical that has been optimized in terms of pharmacological and pharmacokinetic properties and may be therefore advantageous in treatment of metastatic castrate-resistant prostate cancer. In this image, we present the case of an 86-year-old man with metastastic castrate-resistant prostate cancer undergoing 177 Lu-PSMA-I&T treatment. After initial partial response to radioligand therapy, another 2 treatment cycles resulted in a rising serum PSA level that could be correlated with increasingly PSMA-positive as well as a new bone lesion. Consequently, the patient was changed to 177 Lu-rhPSMA-10.1 treatment on a compassionate use basis achieving a renewed tumor response.

2. Australia pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study). [2023] Lutetium-177 (Lu-177) prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is a promising therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is limited data of its efficacy and safety in Asian population. We aim to explore the clinical outcomes of Lu-177 PSMA-RLT in this population.

3. Germany pubmed.ncbi.nlm.nih.gov

Delayed response after repeated 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer. [2021] Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA.

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

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. [2018] Radioligand therapy (RLT) with Lu-177-labeled PSMA-ligands is a new therapy option for prostate cancer. Biodistribution in normal tissues is of interest for therapy planning. We evaluated if the biodistribution of Ga-68-PSMA-11 is influenced by tumor load.

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

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. [2023] This study investigates the predicting factors of the biochemical response and survival of patients with advanced metastatic prostate cancer who underwent therapy with radioligand lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA), often referred to as [177Lu]Lu-PSMA. This study is a review of the previous literature. This study included articles published in the last 10 years in the English language. According to the literature review, treatment with [177Lu]Lu-PSMA has a positive impact on prostate-specific antigen (PSA) within the first cycle and a negative impact on lymph node metastasis. There is a plausible positive impact on PSA after multiple cycles and performance status and a negative impact on visceral metastasis. In conclusion, the reviews show that treatment with [177Lu]Lu-PSMA in patients with castration-resistant prostate cancer is beneficial in reducing PSA and metastasis.

6. Australia pubmed.ncbi.nlm.nih.gov

Lu177-PSMA therapy for men with advanced prostate cancer: Initial 18 months experience at a single Australian tertiary institution. [2020] Lutetium-177-PSMA (LuPSMA) is a targeted systemic radioligand treatment for metastatic castration-resistant prostate cancer (mCRPC). LuPSMA is considered as an experimental treatment not yet used in routine practice. Here, we report our experience following the introduction of LuPSMA therapy at our institution.

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

An Improved 211At-Labeled Agent for PSMA-Targeted α-Therapy. [2022] α-Particle emitters targeting the prostate-specific membrane antigen (PSMA) proved effective in treating patients with prostate cancer who were unresponsive to the corresponding β-particle therapy. 211At is an α-emitter that may engender less toxicity than other α-emitting agents. We synthesized a new 211At-labeled radiotracer targeting PSMA that resulted from the search for a pharmacokinetically optimized agent. Methods: A small series of 125I-labeled compounds was synthesized from tin precursors to evaluate the effect of the location of the radiohalogen within the molecule and the presence of lutetium in the chelate on biodistribution. On that basis, 211At-3-Lu was selected and evaluated in cell uptake and internalization studies, and biodistribution and PSMA-expressing (PSMA+) PC3 PIP tumor growth control were evaluated in experimental flank and metastatic (PC3-ML-Luc) models. A long-term (13-mo) toxicity study was performed for 211At-3-Lu, including tissue chemistries and histopathology. Results: The radiochemical yield of 211At-3-Lu was 17.8% ± 8.2%. Lead compound 211At-3-Lu demonstrated total uptake within PSMA+ PC3 PIP cells of 13.4 ± 0.5% of the input dose after 4 h of incubation, with little uptake in control cells. In SCID mice, 211At-3-Lu provided uptake that was 30.6 ± 4.8 percentage injected dose per gram (%ID/g) in PSMA+ PC3 PIP tumor at 1 h after injection, and this uptake decreased to 9.46 ± 0.96 %ID/g by 24 h. Tumor-to-salivary gland and tumor-to-kidney ratios were 129 ± 99 at 4 h and 130 ± 113 at 24 h, respectively. Deastatination was not significant (stomach, 0.34 ± 0.20 %ID/g at 4 h). Dose-dependent survival was demonstrated at higher doses (>1.48 MBq) in both flank and metastatic models. There was little off-target toxicity, as demonstrated by hematopoietic stability, unchanged tissue chemistries, weight gain rather than loss throughout treatment, and favorable histopathologic findings. Conclusion: Compound 211At-3-Lu or close analogs may provide limited and acceptable toxicity while retaining efficacy in management of prostate cancer.

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

Lutetium-177 Prostate Specific Membrane Antigen Therapy in a Patient With Double Malignancy and Single Functioning Kidney: A Case Report. [2023] Lutetium-177 labeled with 617 types of Prostate Specific Membrane Antigen (177Lu PSMA-617) Radio-ligand Therapy (RLT) is an emerging modality of choice for the treatment of metastatic castration-resistant prostate carcinoma (mCRPC). After it is administered intravenously, it is excreted primarily through the kidneys. Physiological excretion and concomitant expression of PSMA receptors on renal tissues are associated with potential renal toxicity, a matter of concern while treating patients with multiple doses of RLT. There are published articles that have demonstrated the safe use of 177Lu PSMA-617 in patients with bilateral fair-functioning kidneys; however, only a single study has been published that has evaluated its safety in patients with solitary-functioning kidneys. The uniqueness of this case report lies in the fact that we have documented the renal safety profile of 177Lu PSMA-617 therapy after multiple doses in a patient who presented with double malignancy (metastatic castration-resistant prostate carcinoma and left renal cell carcinoma) and had a single-functioning right kidney.

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] In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

10. France pubmed.ncbi.nlm.nih.gov

Real-World Data Analysis of Efficacy and Survival After Lutetium-177 Labelled PSMA Ligand Therapy in Metastatic Castration-Resistant Prostate Cancer. [2021] Label="BACKGROUND">Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA) radioligand therapy is emerging as a promising treatment for metastatic castration-resistant prostate cancer refractory to established therapies. While there is an increasing body of survival and other data from retrospective analyses and prospective trials, there is no clear understanding of how best to predict therapy response and survival outcomes.