Targeted Treatment for Prostate Cancer

(PREDICT Trial)

Recruiting at 74 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if genetic testing can guide the best treatment for prostate cancer patients. Researchers will evaluate various treatments, including valemetostat tosylate (a new potential drug), carboplatin, cabazitaxel, abiraterone acetate, enzalutamide, and a specialized radiation treatment called Lutetium Lu 177 vipivotide tetraxetan. The objective is to assess whether targeting treatments based on a person's cancer genetics can slow or shrink the cancer. Suitable candidates for this trial include those with metastatic prostate cancer who have already undergone certain cancer therapies. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Previous studies found valemetostat tosylate to be safe and manageable for patients, with most experiencing only mild side effects. For those considering carboplatin and cabazitaxel together, research shows this combination is safe, though some experienced more frequent side effects. These side effects were usually not severe enough to stop treatment for most patients.

Abiraterone acetate has been widely used, and studies show it does not significantly increase the risk of serious side effects. Enzalutamide is another well-researched drug, mostly causing manageable side effects.

Lutetium Lu 177 vipivotide tetraxetan is also considered safe, though there is a small risk of serious blood issues. This risk is rare, but it's important to be aware of it.

While these treatments have shown safety in studies, individual experiences may vary. Always consult a doctor to understand what this might mean for each patient. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they offer targeted and innovative approaches that differ from the standard treatments like hormone therapy, chemotherapy, or surgery. Valemetostat tosylate stands out with its targeted action on specific genetic mutations, potentially enhancing precision in treatment. Cabazitaxel combined with carboplatin offers a powerful dual-chemotherapy approach that could provide an edge in aggressive cases. Furthermore, the flexibility in the physician choice arm, with treatments like Lutetium Lu 177 vipivotide tetraxetan, introduces a novel radioligand therapy that directly targets cancer cells, promising a new avenue for tackling resistant prostate cancer.

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

This trial will evaluate several treatments for prostate cancer. Research has shown that valemetostat tosylate, which participants in Arm A may receive, was not effective for prostate cancer but did help with other cancer types. In Arm B, participants will receive a combination of carboplatin and cabazitaxel, which has led to better results in prostate cancer; one study showed a 20.8% higher chance of reducing prostate-specific antigen (PSA) levels. Cabazitaxel alone, which may be chosen in Arm C, has also been successful, helping patients live longer compared to other treatments. Abiraterone acetate, another option in Arm C, has performed well in many studies, achieving its goals 89% of the time. Enzalutamide, also available in Arm C, has been shown to lower the risk of death by 33% in prostate cancer patients. Lastly, lutetium Lu 177 vipivotide tetraxetan, another treatment option in Arm C, has shown promise in slowing disease progression in more than half of the patients studied. ^{4 6 7 8 9}

Who Is on the Research Team?

Rana McKay, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8105236/

Real-World Safety and Efficacy Outcomes with Abiraterone ... Real-world data from this registry confirm the efficacy and safety of first- and second-line abiraterone acetate in patients with mCRPC, including a subset who ...

2. e-juo.org e-juo.org/journal/view.php?number=594

Assessing Patient Risk, Benefit, and Outcomes in Drug ... Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1130634325001023

Low-dose abiraterone acetate for the treatment of prostate ... This study provides evidence supporting the use of low-dose abiraterone in patients with metastatic prostate cancer, showing survival and ...

4. nature.com nature.com/articles/s41391-024-00816-0

Real-world overall survival with abiraterone acetate versus ... Comparison of real-life data of abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer. Sci Rep. 2021;11:14131.

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.5_suppl.367

Real-world discontinuation and efficacy data of abiraterone ... Background: Data from STAMPEDE trial confirmed Overall survival benefit for patients with high-risk localized or locally advanced prostate ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40940844/

The Safety of Abiraterone Acetate in Patients with Metastatic ... Conclusions: In this IPD meta-analysis, abiraterone acetate provides no greater risk of SAE in those receiving abiraterone than those receiving ...

7. mdpi.com mdpi.com/2072-6694/17/17/2747

The Safety of Abiraterone Acetate in Patients with ... We observed a higher incidence of overall adverse events with the use of abiraterone acetate (98.4%) compared to (97.3%), though given the distribution of ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704174

Abiraterone plus Prednisone in Metastatic, Castration- ... The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468294218300583

Abiraterone in metastatic castration-resistant prostate cancer Adverse mineralocorticoid effects (hypokalemia, peripheral edema, hypertension, cardiac failure) and transaminase increase have been reported in pivotal trials.