Targeted Radiation + Therapy for Metastatic Prostate Cancer

Recruiting at 2 trial locations

Overseen By Matthew B Rettig, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Herbal products

Disqualifiers: Visceral metastases, Small cell carcinoma, Active infection, 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: Unknown

Duration: 6 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating metastatic castration-resistant prostate cancer. It combines two treatments: a precise form of radiation therapy and a targeted radiopharmaceutical therapy (PSMA Targeted Radiopharmaceutical Therapy, which delivers radiation directly to cancer cells). The researchers aim to determine if stopping hormone therapy and potentially restoring testosterone can be effective. The trial seeks men with prostate cancer that has spread to bones or soft tissue and continues to grow despite low testosterone levels.

As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important advancements in prostate cancer treatment.

Will I have to stop taking my current medications?

The trial requires that any anti-neoplastic therapies for prostate cancer be completed more than 2 weeks before starting the study treatment. Investigational agents must be completed more than 4 weeks before starting. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Research has shown that PSMA-targeted radiopharmaceutical therapy is generally well-tolerated, typically not causing severe side effects. Studies indicate it has low toxicity. Patients with advanced prostate cancer have responded positively, experiencing less pain and showing good results in scans.

Stereotactic ablative radiotherapy (SABR) is also considered safe. This precise radiation therapy targets cancer cells while sparing healthy tissue. Most patients experience few serious side effects, with less than 5% facing severe reactions, making SABR a generally safe option for treating metastatic cancer.

Both treatments have proven effective while keeping side effects manageable. This trial aims to evaluate their combined effectiveness for prostate cancer patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they focus on a novel approach for metastatic prostate cancer by combining PSMA Targeted Radiopharmaceutical Therapy with Stereotactic Ablative Radiotherapy. Unlike traditional treatments such as hormone therapy or chemo, these therapies specifically target prostate-specific membrane antigen (PSMA) on cancer cells, potentially leading to more precise and effective treatment. Additionally, one arm of the treatment allows for the restoration of physiologic testosterone, which could improve the quality of life for patients by reducing some of the side effects associated with traditional hormone therapies. This dual approach aims to not only control the cancer more effectively but also enhance the patient's overall well-being.

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

Research shows that PSMA-targeted radiopharmaceutical therapy using Lutetium-177 has promising results for treating advanced prostate cancer that no longer responds to hormone therapy. Studies have found that this treatment can lead to good response rates, less pain, and few side effects. Additionally, stereotactic ablative radiotherapy, a precise type of radiation therapy, has effectively controlled cancer, with studies showing strong long-term survival rates. In this trial, participants in both arms will receive a combination of PSMA radiopharmaceutical therapy and stereotactic ablative radiotherapy. Together, these treatments may offer a powerful way to fight prostate cancer by directly targeting cancer cells and helping manage the disease overall. ^{1 2 3 4 6}

Who Is on the Research Team?

Nicholas George Nickols, MD PhD

Principal Investigator

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that's resistant to hormone therapy can join this trial. They must be fit enough for treatment (ECOG PS 0-2), have metastatic disease confirmed by scans, and agree to use contraception. Men who've had certain treatments or surgeries recently, those with specific other cancers within the last two years, or severe psychiatric issues cannot participate.

Inclusion Criteria

My scans show a cancer spot more active than my liver.

I have been treated with specific prostate cancer medications for at least 4 weeks.

There is evidence of soft tissue metastases on CT or MRI scans.

Exclusion Criteria

My cancer is confirmed as small cell/neuroendocrine by specific testing, not just by the presence of certain markers.

I have recovered from side effects of previous treatments to my normal or mild condition.

I have recovered from major surgery complications within the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic ablative radiotherapy and PSMA targeted radiopharmaceutical therapy with cessation of castration

6 months

Testosterone Replacement

Half of the participants receive testosterone replacement therapy following treatment

up to 2 years

Follow-up

Participants are monitored for progression-free survival, objective response rate, and overall survival

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• PSMA Targeted Radiopharmaceutical Therapy
• Stereotactic Ablative Radiotherapy
• Testosterone Replacement

Trial Overview The study is testing if stopping hormone therapy and adding testosterone replacement after targeted radiation therapies can effectively treat advanced prostate cancer. Patients will receive stereotactic ablative radiotherapy and a radiopharmaceutical called Pluvicto; half will also get testosterone replacement.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 3 Interventions

Metastasis directed therapy with stereotactic ablative radiotherapy to all detectable sites of disease plus PSMA radiopharmaceutical therapy and discontinuation of castration, followed by restoration of physiologic testosterone

Group II: Arm 1 Experimental Treatment 2 Interventions

Metastasis directed therapy with stereotactic ablative radiotherapy to all detectable sites of disease plus PSMA radiopharmaceutical therapy and discontinuation of castration

PSMA Targeted Radiopharmaceutical Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Approved in European Union as Lutetium-177 PSMA Therapy for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

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]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of [177Lu]Lu-PSMA-617 to standard care significantly delayed the time to first symptomatic skeletal event, with a median of 11.5 months compared to 6.8 months for standard care alone.

Patients receiving [177Lu]Lu-PSMA-617 also reported improved health-related quality of life and less pain, although there were some serious adverse events, including hematological issues, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Fizazi, K., Herrmann, K., Krause, BJ., et al.[2023]

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is an approved treatment for adult patients with advanced prostate cancer that expresses the prostate-specific membrane antigen (PSMA).

This therapy is specifically indicated for patients who have already undergone treatment with androgen receptor pathway inhibitors and taxane-based chemotherapy, highlighting its role in later-stage cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Metastatic Castration-Resistant Prostate Cancer. Aschenbrenner, DS.[2022]

177Lu-vipivotide tetraxetan is a targeted radiopharmaceutical that effectively treats metastatic castration-resistant prostate cancer (mCRPC) by delivering beta-radiation directly to cancer cells, demonstrating safety and tolerability in clinical trials.

Approved by the FDA in March 2022 based on the VISION trial, this therapy is particularly beneficial for patients who have already undergone androgen receptor pathway inhibition and taxane-based chemotherapy, highlighting its role as a new treatment option in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. Shah, H., Ravi, P., Sonpavde, G., et al.[2023]

Lutetium Lu 177 vipivotide tetraxetan (PLUVICTO™) is a targeted radioligand therapy approved in the USA for treating metastatic castration-resistant prostate cancer (mCRPC) that expresses prostate-specific membrane antigen (PSMA), based on positive results from the phase 3 VISION trial.

This therapy specifically targets PSMA, which is overexpressed in prostate cancer cells, allowing for a more effective treatment option for patients who have already undergone other therapies like androgen receptor inhibition and taxane-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Keam, SJ.[2022]

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is the first FDA-approved targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC), specifically for patients with high levels of prostate-specific membrane antigen (PSMA).

This treatment works by binding to PSMA, which is overexpressed in prostate cancer cells, allowing targeted radiation to damage DNA and induce cell death, making it a promising option in precision medicine for individualized cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Liu, X., Fang, GC., Lu, H., et al.[2023]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107322

Lutetium-177–PSMA-617 for Metastatic Castration ... This radioligand therapy has been associated with encouraging biochemical and radiographic response rates, reduced pain, and low toxicity in multiple early- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9803619/

Therapeutic Outcomes of 177Lu-PSMA Targeted Therapy ... The outcomes of 177Lu-PSMA targeted therapy have demonstrated an acceptable response rate in the metastatic castration-resistant prostate cancer (mCRPC) (5). It ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251923

Outcomes of [177Lu] Lu-PSMA-617 Re-Treatment in ... Results: A total of 589 patients underwent [177Lu] Lu-PSMA-617 RLT, of whom 20 (3.4%, 20/589) received RLT retreatment. The median age was 71.3 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1558767325000989

Safety and Efficacy of Lutetium-177 PSMA Therapy for ... When combined with standard therapy, lutetium-177 PSMA-617 is well tolerated and more effective than standard treatment alone in patients with advanced PSMA- ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.82

Survival outcomes of patients (pts) with metastatic ... Survival outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177-PSMA-617 (Lu) based on ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40752988/

Outcomes for [ 177 Lu]Lu-PSMA-617 with and Without ... This study aimed to assess the efficacy of [177Lu]Lu-PSMA-617 in patients with and without the concurrent use of an ARPI. Methods: We analyzed ...