Radioligand + Radiation Therapy for Prostate Cancer

Overseen By Ashesh B. Jani, MD, MSEE, FASTRO

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Emory University

Disqualifiers: Inflammatory bowel disease, Metastasis, Myelosuppression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 2

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat prostate cancer that has returned after surgery. It combines two treatments: a targeted radioactive drug, Lutetium Lu 177 PSMA-10.1, which directly attacks cancer cells, and radiation therapy, which uses high-energy rays to kill cancer cells. The trial aims to assess the safety of this combination and determine the optimal dose. Men who have undergone prostate surgery and now experience rising PSA levels, indicating cancer recurrence, might consider participating. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 177Lu-rhPSMA-10.1, a type of targeted radiation therapy, is generally well-tolerated. In studies, this treatment produced promising results. Many patients experienced a significant drop in their prostate-specific antigen (PSA) levels, which can indicate cancer activity. Importantly, most patients did not suffer severe side effects. This suggests that 177Lu-rhPSMA-10.1 could be a safe option for those with recurring prostate cancer after surgery. However, as this trial is in an early stage, ongoing studies aim to confirm these findings and determine the best dose. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Lutetium Lu 177 PSMA-10.1 with radiation therapy for prostate cancer because it targets cancer cells more precisely. Unlike traditional treatments like chemotherapy or hormone therapy, which can affect both healthy and cancerous cells, this approach uses a radioactive compound that binds specifically to the prostate-specific membrane antigen (PSMA) found on cancer cells. This precision allows for targeted radiation delivery, potentially leading to fewer side effects and more effective tumor reduction. Additionally, the integration of advanced imaging techniques, such as PET/CT and SPECT-CT, enhances the ability to monitor treatment response, providing a clearer picture of its effectiveness.

What evidence suggests that this trial's treatments could be effective for recurrent prostate cancer?

Research has shown that 177Lu-rhPSMA-10.1, administered alongside External Beam Radiation Therapy (EBRT) in this trial, can significantly slow tumor growth. Studies have found that it targets prostate cancer cells by delivering radiation directly to the tumor, while mostly sparing healthy tissues. In patients with advanced prostate cancer, this treatment significantly lowered levels of prostate-specific antigen, a marker used to monitor the cancer. The treatment effectively balances attacking the tumor and protecting healthy organs, offering promise for controlling cancer. Overall, these findings suggest that 177Lu-rhPSMA-10.1 could be a viable option for treating prostate cancer that recurs after surgery. ^{1 3 6 7 8}

Who Is on the Research Team?

David M. Schuster, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• External Beam Radiation Therapy
• Lutetium Lu 177 PSMA-10.1

Trial Overview 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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Lutetium-177 PSMA radioligand therapy shows a significant response rate in treating metastatic castration-resistant prostate cancer, with 56% of patients experiencing a PSA decline of 50% or more, indicating its efficacy as a treatment option.

The therapy has a low toxicity profile, with serious adverse events occurring in a small percentage of patients, and is particularly effective in those with lymph node metastases and lower baseline PSA levels, suggesting these factors can help predict better survival outcomes.

NCBI (Pubmed)

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. Meyrick, D., Gallyamov, M., Sabarimurugan, S., et al.[2021]

In an 18-month study involving 50 patients with metastatic castration-resistant prostate cancer (mCRPC), 44.9% experienced a significant decline in prostate-specific antigen (PSA) levels of 50% or more after receiving up to four cycles of Lutetium-177-PSMA (LuPSMA) therapy.

The treatment was found to be safe, with most adverse events being mild (grade I), indicating that LuPSMA could be a promising option for patients who have exhausted other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lu177-PSMA therapy for men with advanced prostate cancer: Initial 18 months experience at a single Australian tertiary institution. McBean, R., O'Kane, B., Parsons, R., et al.[2020]

The new 211At-labeled radiotracer, 211At-3-Lu, effectively targets prostate-specific membrane antigen (PSMA) in prostate cancer cells, showing significant uptake in PSMA+ tumors with minimal uptake in non-target cells, indicating its potential for targeted therapy.

In a long-term toxicity study, 211At-3-Lu demonstrated low off-target toxicity and favorable safety profiles, including stable hematopoietic function and positive histopathological outcomes, suggesting it could be a safe and effective treatment option for patients with prostate cancer resistant to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Improved 211At-Labeled Agent for PSMA-Targeted α-Therapy. Mease, RC., Kang, CM., Kumar, V., et al.[2022]

In a study of 135 prostate cancer patients, those with high tumor loads showed significantly reduced uptake of Ga-68-PSMA-11 in critical organs like the lacrimal and salivary glands, which could impact treatment planning for radioligand therapy (RLT).

The findings suggest that individualizing therapy protocols based on diagnostic PSMA PET imaging could enhance the efficacy and safety of Lu-177-labeled PSMA-ligand therapy, as reduced tracer uptake in dose-limiting organs may affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. Gaertner, FC., Halabi, K., Ahmadzadehfar, H., et al.[2018]

Treatment with lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA) significantly reduces prostate-specific antigen (PSA) levels in patients with advanced metastatic prostate cancer, especially after the first treatment cycle.

The therapy shows a beneficial effect on reducing lymph node metastasis, while also indicating potential negative impacts on visceral metastasis, highlighting its efficacy in managing certain aspects of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. Rathore, R., Rangrej, SB., Kieme, I., et al.[2023]

177 Lu-rhPSMA-10.1 is a new radiopharmaceutical designed to target PSMA, showing promise in treating metastatic castrate-resistant prostate cancer, particularly in patients who have not responded to previous therapies.

In a case study of an 86-year-old man, switching to 177 Lu-rhPSMA-10.1 after initial treatment failure led to a renewed tumor response, suggesting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

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. Bundschuh, RA., Pfob, CH., Wienand, G., et al.[2023]

In a study of 71 patients with metastatic castration-resistant prostate cancer, 56% experienced a significant PSA decline of 50% or more after receiving three cycles of Lutetium-177 labeled PSMA-617 radioligand therapy, indicating its efficacy as a treatment option.

The therapy demonstrated delayed responses, as 28 out of 30 patients who responded after the first cycle continued to show positive results, and 12 out of 41 initial non-responders responded to subsequent cycles, highlighting the potential for ongoing therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed response after repeated 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer. Rahbar, K., Bögeman, M., Yordanova, A., et al.[2021]

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]

177Lu PSMA-617 Radio-ligand Therapy is a promising treatment for metastatic castration-resistant prostate carcinoma, but it poses potential renal toxicity due to its excretion through the kidneys.

This case report highlights the renal safety of administering multiple doses of 177Lu PSMA-617 in a patient with a solitary-functioning kidney, suggesting that it can be safely used even in patients with compromised renal function.

NCBI (Pubmed)

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. Naeem, Z., Zahra, UB., Numair Younis, M., et al.[2023]

In a study of 84 Asian patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Lutetium-177 PSMA radioligand therapy, the median overall survival was 12.2 months and the median PSA progression-free survival was 5.2 months, indicating promising efficacy.

A significant 51.8% of patients experienced a PSA decline of 50% or more, which was linked to longer overall survival and PSA progression-free survival, while the treatment showed a manageable safety profile with grade 3 hematotoxicity occurring in 13 out of 78 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study). Chua, WM., Lam, WW., Tong, AK., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40049746/

Preclinical Evaluation of 177 Lu-rhPSMA-10.1, a ... When efficacy was evaluated, 177Lu-rhPSMA-10.1 significantly suppressed tumor growth versus vehicle from day 11 (P < 0.05) in LNCaP xenografts ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/66/4/599

Preclinical Evaluation of 177 Lu-rhPSMA-10.1, a ... Our data showed 177Lu-rhPSMA-10.1 to significantly reduce tumor growth in a dose-dependent manner, with even 15 MBq of 177Lu-rhPSMA-10.1 ...

3. onclive.com onclive.com/view/177lu-rhpsma-10-1-injection-generates-favorable-radiation-dosimetry-data-in-mcrpc

177Lu rhPSMA-10.1 Injection Generates Favorable ... 177Lu rhPSMA-10.1 injection led to proportionally higher absorbed radiation doses in tumors vs healthy tissues in patients with mCRPC.

4. urologytimes.com urologytimes.com/view/177lu-rhpsma-10-1-injection-shows-positive-radiation-dosimetry-results-in-mcrpc

177Lu-rhPSMA-10.1 injection shows positive radiation ... The results demonstrated a favorable ratio between radiation doses absorbed in the tumor vs the doses delivered to key healthy organs.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38164586/

First Safety and Efficacy Data with the Radiohybrid 177Lu- ... Results: The patients received a total activity of 29.6-59.4 GBq (4-6 cycles). Prostate-specific antigen was reduced by 100%, 99%, 88%, and 35%.

6. jnm.snmjournals.org jnm.snmjournals.org/content/65/3/432

First Safety and Efficacy Data with the Radiohybrid 177Lu ... Our data show that 177Lu-rhPSMA-10.1 was well tolerated and induced a profound PSA response in 3 of 4 patients, with a smaller PSA response in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12491383/

Organ and tumour dosimetry of 177Lu-rhPSMA-10.1, a novel ... First safety and efficacy data with the radiohybrid 177Lu-rhPSMA-10.1 for the treatment of metastatic prostate cancer. J Nucl Med. 2024;65 ...

8. urologytimes.com urologytimes.com/view/phase-1-data-show-encouraging-safety-of-177lu-rhpsma-10-1-injection-in-mcrpc

Phase 1 data show encouraging safety of 177Lu-rhPSMA- ... Lutetium ( 177 Lu) rhPSMA-10.1 injection demonstrated promising radiation dosimetry results in patients with metastatic castration-resistant prostate cancer ( ...