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

Trial Summary

What is the purpose of this trial?

This trial tests if the combination of comprehensive metastasis directed therapy delivered by a precision form of external beam radiotherapy (stereotactic ablative radiotherapy), combined with PSMA targeted radiopharmaceutical therapy and cessation of castration, and then followed by testosterone replacement, is an effective treatment for metastatic castration resistant prostate cancer. All patients will be treated with stereotactic ablative radiotherapy and PSMA targeted radiopharmaceutical therapy with cessation of castration. Half of patients are randomized to either receive, or not receive, subsequent testosterone replacement.

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.

What data supports the effectiveness of the drug Lutetium-177 vipivotide tetraxetan for metastatic prostate cancer?

The drug Lutetium-177 vipivotide tetraxetan has been shown to improve survival and quality of life in patients with metastatic castration-resistant prostate cancer, as demonstrated in the phase 3 VISION trial. It targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to them, which helps to kill the cancer cells while sparing normal tissues. ^{1 2 3 4 5}

Is Lutetium-177 PSMA Therapy safe for humans?

Lutetium-177 PSMA Therapy, also known as Pluvicto, has been approved by the FDA for treating certain prostate cancers, indicating it has been evaluated for safety. It targets cancer cells specifically, which helps minimize damage to normal tissues, suggesting a favorable safety profile. ^{1 2 4 5 6}

What makes this treatment for metastatic prostate cancer unique?

This treatment is unique because it uses a targeted radioligand therapy called Lutetium-177 PSMA, which specifically binds to prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to the tumor and minimizing damage to normal tissues. It is the first FDA-approved therapy of its kind for prostate cancer, offering a more personalized approach to treatment. ^{1 2 3 4 7}

Research Team

Nicholas George Nickols, MD PhD

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. Spain pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. [2023]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. [2023]

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

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

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

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023]

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

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