Targeted Treatment for Prostate Cancer

(PREDICT Trial)

Recruiting at 28 trial locations

Overseen By Shiva Baghaie

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Androgen receptor inhibitors

Must not be taking: EZH inhibitors, CYP3A inducers

Disqualifiers: Brain metastases, Cardiovascular issues, 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: Up to 1 year

474 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial evaluates whether genetic testing in prostate cancer is helpful in deciding which study treatment patients are assigned. Patient cancer tissue samples are obtained from a previous surgery or biopsy procedure and tested for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) abnormalities or mutations in their cancer. Valemetostat tosylate is in a class of medications called EZH1/EZH2 inhibitors. It blocks proteins called EZH1 and EZH2, which may help slow or stop the spread of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Cabazitaxel injection is in a class of medications called microtubule inhibitors. It works by slowing or stopping the growth of tumor cells. Abiraterone acetate blocks tissues from making androgens (male hormones), such as testosterone. This may cause the death of tumor cells that need androgens to grow. It is a type of anti-androgen. Enzalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Lutetium Lu 177 vipivotide tetraxetan is in a class of medications called radiopharmaceuticals. It works by targeting and delivering radiation directly to tumor cells which damages and kills these cells. Assigning patients to targeted treatment based on genetic testing may help shrink or slow the cancer from growing

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before registration. Specifically, you must not have taken any cytotoxic, biologic, radiopharmaceutical, or other non-kinase inhibitor investigational agents within 4 weeks of registration, and certain small molecular kinase inhibitors within 2 weeks. Additionally, you must stop taking abiraterone acetate, apalutamide, or darolutamide within 2 weeks, and enzalutamide within 4 weeks of registration.

What data supports the effectiveness of the drug Lutetium Lu 177 Vipivotide Tetraxetan for prostate cancer?

The drug Lutetium Lu 177 Vipivotide Tetraxetan has been shown to improve survival and quality of life in patients with advanced prostate cancer, as it targets and destroys cancer cells by binding to a specific protein found in high amounts on these cells. It was approved by the FDA based on its effectiveness in treating prostate cancer that has spread and is resistant to other treatments. ^{1 2 3 4 5}

Is Lutetium Lu 177 Vipivotide Tetraxetan safe for humans?

Lutetium Lu 177 vipivotide tetraxetan 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 3 4 6}

What makes the drug Lutetium Lu 177 vipivotide tetraxetan unique for prostate cancer treatment?

Lutetium Lu 177 vipivotide tetraxetan is unique because it is the first FDA-approved targeted radioligand therapy for prostate cancer, specifically designed to bind to prostate-specific membrane antigen (PSMA) on cancer cells, delivering targeted radiation to kill these cells while sparing most normal tissues. ^{1 2 3 4 7}

Research Team

Rana McKay, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

Adults with prostate cancer, including those with specific variant histologies, are eligible if they have evidence of disease progression. They must have rising PSA levels or radiographic/bone metastasis progression and tissue available for genetic testing. Prior treatment with certain hormone therapies or taxane is required unless ineligible or refused by the patient.

Inclusion Criteria

My prostate cancer has spread to my bones and is getting worse.

My prostate cancer diagnosis is confirmed by lab tests.

My cancer can be measured or seen on scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genetic Testing

Patients undergo genetic testing on previously-collected tissue samples to determine treatment arm assignment

1-2 weeks

Treatment

Patients receive treatment based on genetic testing results, with different regimens for each arm. Treatment cycles repeat every 21 to 42 days depending on the regimen, in the absence of disease progression or unacceptable toxicity.

Up to 1 year

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment. Patients without disease progression are followed every 2 months for the first 6 months and then every 3 months for up to 5 years. Patients with disease progression are followed every 6 months for 5 years.

Up to 5 years

Treatment Details

Interventions

• Abiraterone Acetate
• Cabazitaxel
• Carboplatin
• Enzalutamide
• Lutetium Lu 177 Vipivotide Tetraxetan
• Valemetostat Tosylate

Trial Overview The trial tests targeted treatments based on genetic abnormalities in prostate cancer cells. Treatments include various medications that inhibit tumor growth through different mechanisms, such as blocking male hormones or delivering radiation directly to tumor cells.

Participant Groups

Group I: Arm C (genetic testing, physician choice treatment) Experimental Treatment 11 Interventions

Patients undergo genetic testing on previously-collected tissue. Patients receive one of the following treatment regimens per treating physician: 1)Cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. 2)Abiraterone acetate PO QD on days 1-28 of each cycle and prednisone PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 3) Enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 4) Lutetium Lu 177 vipivotide tetraxetan IV on day 1 of each cycle. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.

Group II: Arm B (genetic testing, carboplatin, cabazitaxel) Experimental Treatment 9 Interventions

Patients undergo genetic testing on previously-collected tissue samples. Patients receive carboplatin IV over 30 minutes and cabazitaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.

Group III: Arm A (genetic testing, valemetostat tosylate) Experimental Treatment 8 Interventions

Patients undergo genetic testing on previously-collected tissue samples. Patients receive valemetostat tosylate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT and bone scan throughout the trial. Patients may also undergo optional FDG or PSMA PET, as well as optional blood collection throughout the trial.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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]

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]

The VISION trial demonstrated that lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) significantly improves progression-free and overall survival in patients with metastatic castration-resistant prostate cancer compared to standard of care (SoC).

In terms of cost-effectiveness, 177Lu-PSMA-617 therapy resulted in an incremental cost-effectiveness ratio of $200,708 per quality-adjusted life year (QALY), indicating that while it is more expensive than SoC, it may still be considered cost-effective under certain willingness-to-pay thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer. Mehrens, D., Kramer, KKM., Unterrainer, LM., 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

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

4. 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]

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

Novel PSMA-Targeting Radionuclide Peptidomimetics for Treating Prostate Cancer. [2023]

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

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

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

Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer. [2023]