Clinical Trials for Prostate Cancer: Treatment Studies and Enrollment

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Prostate cancer is the most common cancer in US men and has seen significant therapeutic advances through hormonal therapies, PARP inhibitors for BRCA-mutated disease, theranostic radiopharmaceuticals like Lu-177 PSMA, and emerging immunotherapy and targeted approaches. The treatment landscape varies enormously by stage and disease characteristics — localized prostate cancer has different options than metastatic castration-resistant disease. For patients across the spectrum, clinical trials for prostate cancer can offer access to advanced and emerging therapies. This guide explains what a clinical trial actually is, how the phases work, how to search for prostate cancer trials in 2026, what eligibility and enrollment involve, and how to weigh a trial with your own care team. Considering a trial does not mean you have run out of options, and it is not a sign that your current treatment has failed — trials exist at every stage of disease.

What is a clinical trial?

A clinical trial is a carefully designed research study that tests whether a new approach — a drug, a dose, a device, a combination, a surgical or radiation technique, or a screening or surveillance strategy — is safe and how well it works in people. Trials follow a written plan called a protocol, are reviewed by an institutional review board (IRB) to protect participants, and are conducted under regulatory oversight. The results help establish the standard treatments that future patients receive.

It is important to understand what a trial is not. A clinical trial is research, not a guaranteed treatment. An experimental therapy may turn out to work better than the current standard, about the same, or less well — that is precisely what the study is trying to find out. Some trials compare a new approach against the current standard of care, and in many cancer trials participants in every group receive active treatment rather than a placebo alone. Your care team can explain how a specific trial is designed before you decide.

The phases of a clinical trial

Cancer treatment trials are generally organized into phases, each answering a different question:

• Phase 1: The first testing of an approach in people. These small studies focus mainly on safety — finding a safe dose range and identifying side effects. Some early-phase prostate cancer trials enroll patients whose disease has progressed on standard therapies.
• Phase 2: Studies that look at whether the treatment has an effect against the cancer (for example, PSA response, imaging response, or delaying progression) while continuing to monitor safety in a larger group.
• Phase 3: Larger studies, often randomized, that compare the new approach against the current standard of care to see whether it is better or has fewer side effects. Phase 3 results frequently support FDA approval.
• Phase 4: Studies conducted after a treatment is approved, to gather more information about long-term safety, benefits, and use in broader populations.

Understanding the phase helps set expectations: a phase 1 trial is primarily about safety and dose, while a phase 3 trial is testing whether an approach should become a new standard. None of the phases guarantees benefit to any individual participant.

Categories of prostate cancer trials

Active prostate cancer trials in 2026 include:

Theranostic radiopharmaceuticals: Lu-177 PSMA-617 (Pluvicto) is approved for PSMA-positive metastatic castration-resistant prostate cancer; in 2025 the FDA expanded its approval to earlier use before chemotherapy in patients previously treated with an androgen receptor pathway inhibitor, based on the phase 3 PSMAfore trial. Ongoing trials test next-generation PSMA-targeted radiopharmaceuticals, alpha-emitters (such as actinium-225), and new combinations.

PARP inhibitors: Olaparib, rucaparib, and other PARP inhibitors are approved for BRCA-mutated prostate cancer; trials test combinations with hormonal therapy and immunotherapy, and use in earlier disease settings.

Next-generation hormonal therapies: Beyond enzalutamide, abiraterone, apalutamide, and darolutamide, trials test newer androgen receptor degraders, AR antagonists, and agents designed to overcome resistance.

Immunotherapy: Standard checkpoint immunotherapy has shown limited activity in unselected prostate cancer, so trials test combinations with hormonal therapy, novel checkpoint inhibitors, bispecific antibodies, and CAR-T approaches in specific subsets.

Localized disease management: Trials testing focal therapy approaches, active surveillance protocols, and de-escalation for low-risk disease.

Hereditary prostate cancer: Studies in men with germline BRCA, ATM, or other DNA repair mutations test specific targeted approaches.

How to search ClinicalTrials.gov and other resources

ClinicalTrials.gov, maintained by the US National Library of Medicine, is the largest public registry of clinical studies. To search it effectively:

• Enter a condition such as “prostate cancer” and add terms for your disease state (for example “metastatic castration-resistant”) or a specific drug or approach.
• Filter by recruitment status (look for “Recruiting” or “Enrolling by invitation”) and by location to find studies near you.
• Read the eligibility criteria, and note the study’s phase and the contact information listed for each site.
• Bring the study’s NCT identification number (for example, NCT followed by eight digits) to your appointment so your doctor can look up the full protocol.

Other trusted starting points include the National Cancer Institute clinical trials search, the Prostate Cancer Foundation and ZERO Prostate Cancer patient resources, NCI-Designated Cancer Centers, and major academic urology and medical oncology programs. Listings can change quickly, so confirm that a study is still open and that you may qualify by contacting the study team directly. Genomic testing of the tumor (or germline testing) is increasingly important for matching, particularly for advanced disease.

Informed consent and your right to withdraw

Before you can enroll in any trial, the study team must take you through informed consent. This is a process, not just a signature: the team explains the study’s purpose, what will be done, the expected time commitment, the potential benefits, the known and possible risks and side effects, any costs, and the alternatives to participating (including standard treatment). You should have time to ask questions and to discuss the study with your own doctor and family.

Participation is always voluntary. You have the right to decline to join, and if you do enroll, you have the right to withdraw at any time, for any reason, without penalty and without losing the medical care you are otherwise entitled to. Ask the study team who to contact with questions or concerns, how your safety will be monitored, and what happens to your care if you leave the study.

Do not stop your current treatment to join a trial

Never stop, change, or delay your current prostate cancer treatment in order to join a trial without first talking to your own urologist or oncologist. Some trials require that you have not recently taken certain therapies, but your care team — not the trial listing — is the right source for deciding whether a study is safe and appropriate for you and how to time any transition. A trial should be considered as part of your overall treatment plan, in coordination with the doctors who already know your case.

Stage-specific trial considerations

Prostate cancer trials are organized by disease stage:

Active surveillance and low-risk localized disease: Trials test surveillance protocols, biomarker monitoring, and selective intervention for low-risk disease that may not need immediate treatment.

Localized intermediate- or high-risk disease: Trials test surgical approaches, radiation techniques, hormonal therapy combinations, and adjuvant therapies after definitive treatment.

Biochemical recurrence: For patients with rising PSA after definitive treatment but no detectable metastases, trials test approaches like salvage radiation, intermittent hormonal therapy, and PSMA imaging-guided treatment.

Metastatic hormone-sensitive prostate cancer (mHSPC): For patients with metastatic disease starting first-line hormonal therapy, trials test triplet combinations and novel agents added to standard ADT plus a next-generation hormonal therapy.

Metastatic castration-resistant prostate cancer (mCRPC): Disease that has progressed despite hormonal therapy — the most active trial area, with many novel agents in testing.

Genomic testing for prostate cancer trials

Key genetic features that can affect trial eligibility:

• BRCA1/BRCA2 mutations (germline or somatic): found in roughly 10–15% of metastatic prostate cancer; may make you eligible for PARP inhibitor trials.
• ATM mutations: some PARP inhibitor activity; specific trials.
• Other DNA damage repair mutations (CHEK2, PALB2, RAD51, and others): variable activity; some trials focus on homologous recombination deficiency.
• MSI-H/MMR-deficient: a small share of advanced prostate cancer; may be eligible for immunotherapy.
• AR mutations and amplifications: may affect hormonal therapy resistance trials.
• PTEN loss: may affect AKT inhibitor trials.

The National Cancer Institute and specialty guidelines generally recommend germline genetic testing for men with metastatic prostate cancer or a significant family history. Most academic medical centers offer comprehensive tumor and germline testing; ask your care team whether it is appropriate for you.

Typical eligibility for prostate cancer trials

Common inclusion criteria:

• Confirmed prostate adenocarcinoma diagnosis
• Stage and disease state matching the trial’s target population
• A specific genomic profile (for targeted-therapy trials)
• Adequate performance status (often ECOG 0–2)
• Adequate organ function
• Castration-sensitive or castration-resistant disease as required
• A specific prior-therapy history

Common exclusion criteria:

• Small cell or neuroendocrine prostate cancer (usually a separate trial track)
• Other active cancers
• Significant cardiac disease
• Active autoimmune disease (for many immunotherapy trials)
• Specific prior therapies that disqualify (varies by trial)

Trials in metastatic castration-resistant disease

mCRPC is the most active prostate cancer trial area. Common trial types:

Lu-177 PSMA combinations: studies testing Pluvicto plus hormonal therapy, plus PARP inhibitors, plus immunotherapy, in earlier lines, and at different doses.

Next-generation PSMA radiopharmaceuticals: alpha-emitters such as Ac-225 PSMA, longer-acting beta-emitters, and combinations.

PARP inhibitor combinations: PARP inhibitors plus next-generation hormonal therapy — for example, niraparib plus abiraterone (Akeega) and talazoparib plus enzalutamide have been approved in defined settings, and other combinations remain in development.

Novel mechanisms: AR degraders, AR antagonists, prostate-specific bispecific antibodies, and prostate-targeted CAR-T approaches.

AKT inhibitors: capivasertib combinations have shown activity in PTEN-altered disease and continue to be tested in expanded settings.

Trials in metastatic hormone-sensitive disease

The mHSPC space has shifted with triplet therapy (ADT plus abiraterone plus docetaxel, or ADT plus darolutamide plus docetaxel) becoming a standard option for high-risk disease. Trials test:

• Genomic-guided variations on triplet therapy
• Adding PARP inhibitors to therapy in BRCA-mutated disease
• Earlier use of Lu-177 PSMA in mHSPC
• Novel agents added to standard combinations

Trials in localized disease

Active surveillance and de-escalation approaches:

• MRI-guided active surveillance protocols
• Biomarker-guided decisions about treatment intensity
• Focal therapy approaches (HIFU, cryoablation, focal radiation)
• Adjuvant therapy after radical prostatectomy
• Radiation technique trials (proton therapy, hypofractionation, brachytherapy combinations)

Frequently Asked Questions

Will I get a placebo instead of treatment?

In most cancer treatment trials, a placebo is not used in place of effective therapy. Placebos, when used, are typically added to standard treatment so that one group receives standard care plus the new agent and the other receives standard care plus placebo. The consent process explains exactly how a given trial is designed, so ask the study team before enrolling.

Do I need genomic testing for prostate cancer trials?

It is strongly encouraged for metastatic disease, particularly to identify BRCA mutations and other DNA damage repair alterations. Germline testing is generally recommended for men with metastatic prostate cancer or a significant family history. Ask your oncologist whether testing is right for you.

Are PARP inhibitor trials only for BRCA-mutated patients?

Most are focused on DNA-repair-mutated disease. Some trials test PARP inhibitors more broadly in mCRPC, though activity outside DNA-repair-mutated disease appears limited. Combination trials may have broader eligibility.

What is Lu-177 PSMA?

It is a radiopharmaceutical that delivers radiation to prostate cancer cells expressing PSMA (prostate-specific membrane antigen). It is approved as Pluvicto for eligible patients with advanced mCRPC, and multiple trials test next-generation versions and combinations.

Does it cost money to join a trial?

The study typically covers the costs of the investigational treatment and study-specific tests, while your insurance may still be billed for routine care you would receive anyway. Costs vary by trial, so ask the study team and your insurer what you would be responsible for before enrolling.

Can I participate if I have had other cancers?

Most trials exclude other active cancers. A history of a treated cancer that is in remission for a specified period (often several years) is frequently allowed, depending on the protocol.

The bottom line on prostate cancer trials

Prostate cancer trials cover the full range from active surveillance to advanced metastatic disease. Theranostic radiopharmaceuticals, PARP inhibitors for BRCA-mutated disease, and next-generation hormonal therapies are major active research areas, and genomic testing is increasingly important for matching, particularly for advanced disease. NCI-Designated Cancer Centers offer the most extensive prostate cancer trial programs. Use ClinicalTrials.gov and the NCI trial finder to identify open studies, but treat those listings as a starting point for a conversation with your care team. Discuss trial options with your urologist or medical oncologist as part of comprehensive treatment planning — especially if you have advanced disease, BRCA mutations, or are weighing active surveillance for low-risk localized disease.

Sources

• ClinicalTrials.gov, US National Library of Medicine (NIH) — clinical trials registry and search
• National Cancer Institute (cancer.gov) — clinical trials search, phases, informed consent, and genetic testing information
• National Institutes of Health (NIH) — patient guidance on participating in clinical research
• US FDA and Novartis media releases — 2025 expanded approval of Pluvicto (Lu-177 PSMA-617) based on the PSMAfore trial