PRL-02 Injection for Prostate Cancer

Recruiting at 22 trial locations

Overseen By Astellas Pharma Global Development, Inc.

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Astellas Pharma Global Development, Inc.

Must be taking: GnRH therapy

Must not be taking: CYP17 inhibitors, AR blockers

Disqualifiers: CNS metastases, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 24

174 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new injection treatment called PRL-02 depot (abiraterone decanoate) for men with advanced prostate cancer that has returned or hasn't responded to past treatments. The main goals are to determine if PRL-02 is safe, tolerable, and to establish the right dose. Some participants will also take enzalutamide to assess the combination's effectiveness. Men who have undergone prostate cancer treatments like hormone therapy but still have cancer that has spread might be suitable candidates. Participants will receive injections every 12 weeks and visit the clinic for regular health checks. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications like anti-androgens, AR blocking agents, and some herbal products must be stopped a few weeks before starting the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research shows that PRL-02, a new treatment being tested for prostate cancer, has undergone safety studies in humans. In earlier studies, researchers administered PRL-02 as a long-lasting injection into the muscle, which helps the medicine remain in the body longer. These studies included men with advanced prostate cancer.

The results indicated that PRL-02 was generally well-tolerated, with most participants not experiencing serious side effects. However, like all treatments, some side effects occurred, but they were usually mild and manageable.

Since PRL-02 is still in early testing, a complete understanding of its safety in humans is not yet available. However, studies so far suggest that PRL-02 could be a promising option for lowering testosterone levels, which helps treat prostate cancer.

For those considering joining a clinical trial, it is important to know that this treatment has shown a reasonable level of safety in early tests. Always discuss any concerns with a doctor or the study team, who can provide more detailed information specific to individual situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

PRL-02 is unique because it uses abiraterone decanoate, a novel formulation that aims to improve upon the standard abiraterone acetate, which is commonly used for prostate cancer. This formulation could potentially enhance stability and absorption, offering more efficient delivery and better patient outcomes. Additionally, PRL-02 is administered as an injection, which may provide a more consistent release of the medication compared to oral options. Researchers are excited about these treatments because they could offer more effective control of cancer progression with potentially fewer side effects and improved quality of life for patients.

What evidence suggests that PRL-02 might be an effective treatment for prostate cancer?

Research shows that PRL-02, a long-lasting injection into the muscle, could be a promising treatment for advanced prostate cancer. Previous studies found that PRL-02 releases abiraterone decanoate, which helps lower testosterone levels in the body. Lowering testosterone is crucial because it can promote the growth of prostate cancer cells. In this trial, participants will receive PRL-02 in different combinations: some with prednisone, others with dexamethasone, and some with additional treatments like enzalutamide. Early results suggest that PRL-02 can help control cancer progression, especially in patients whose cancer hasn't responded well to other treatments. While more research is needed, the initial findings are encouraging for those with advanced prostate cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Central Contact

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

This trial is for men with advanced prostate cancer, including various stages and those who've had hormone therapy. Participants should be relatively fit (ECOG 0 or 1) and may have received certain other treatments like abiraterone or enzalutamide. Men with severe obesity, active heart disease, known allergies to the drugs being tested, uncontrolled diabetes, brain metastases not stable post-treatment, recent chemotherapy, current AR blockers use or estrogens in the last 3 months can't join.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I have had surgery to remove my testicles or have been on hormone therapy for over a month.

My prostate cancer is sensitive or resistant to hormone therapy.

Exclusion Criteria

I have brain metastases but am stable after treatment and not on high-dose steroids.

I am allergic to PRL-02, abiraterone, prednisone, dexamethasone, or their ingredients.

I have not taken estrogen in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of PRL-02 depot with other medications to determine safety and tolerability

12 weeks

Injections every 12 weeks, daily oral medication

Dose Expansion

Participants with prior hormone therapy receive PRL-02 depot to further assess safety and efficacy

12 weeks

Injections every 12 weeks, daily oral medication

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Health checks and scans every few months

What Are the Treatments Tested in This Trial?

Interventions

• abiraterone decanoate
• dexamethasone
• Prednisone
• PRL-02

Trial Overview The study tests PRL-02 injections along with standard medications like prednisone and dexamethasone in men with advanced prostate cancer. It's an early-phase trial to see how well this new treatment works when given as a shot into the muscle. Some patients will also receive docetaxel infusions.

How Is the Trial Designed?

Group I: Phase 1b Dose Expansion: Group E Experimental Treatment 2 Interventions

Participants with mCRPC with prior treatment with 1 of the following androgen receptor pathway inhibitor (ARPIs) (enzalutamide, apalutamide, and/or darolutamide) will receive escalating doses of PRL-02 + dexamethasone.

Group II: Phase 1b Dose Expansion: Group D Experimental Treatment 2 Interventions

Participants with mCRPC with prior treatment with abiraterone acetate will receive escalating doses of PRL-02 + dexamethasone.

Group III: Phase 1a Dose Escalation: Group H Experimental Treatment 3 Interventions

Participants with mCSPC or mCRPC will receive escalating doses of PRL-02 + dexamethasone + enzalutamide.

Group IV: Phase 1a Dose Escalation: Group B Experimental Treatment 2 Interventions

Participants with mCSPC, nmCSPC with biochemical relapse, or mCRPC will receive escalating doses of PRL-02 + dexamethasone.

Group V: Phase 1a Dose Escalation: Group A Experimental Treatment 2 Interventions

Participants with metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical relapse, or metastatic castration-resistant prostate cancer (mCRPC) will receive escalating doses of PRL-02 + prednisone.

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Propella Therapeutics

Lead Sponsor

Trials

3

Recruited

420+

Published Research Related to This Trial

In a pivotal phase III trial, oral abiraterone acetate combined with prednisone significantly improved overall survival and delayed disease progression in patients with metastatic castration-resistant prostate cancer (CRPC) who had previously undergone docetaxel chemotherapy.

While abiraterone acetate showed a generally acceptable safety profile, it was associated with higher rates of specific adverse events, such as cardiac disorders and fluid retention, compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: in metastatic castration-resistant prostate cancer. Yang, LP.[2021]

In a study of 1088 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate combined with prednisone significantly improved radiographic progression-free survival (rPFS) compared to prednisone alone, with a median rPFS of 16.5 months versus 8.2 months.

Abiraterone acetate also showed a trend towards improved overall survival (OS) with a median of 35.3 months compared to 30.1 months for prednisone, indicating a potential benefit in prolonging life, while maintaining a favorable safety profile over long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Rathkopf, DE., Smith, MR., de Bono, JS., et al.[2022]

A 62-year-old patient with metastatic castration-resistant prostate cancer showed a complete response to abiraterone acetate combined with prednisone, achieving significant reductions in prostate-specific antigen levels within 6 months.

Despite having a castrate testosterone level, the patient maintained a relatively high serum testosterone level, indicating that abiraterone acetate can still be effective in such cases, highlighting its potential efficacy even in complex clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically complete response to abiraterone acetate in a patient with metastatic castration-resistant prostate cancer. Yanai, Y., Kosaka, T., Hongo, H., et al.[2022]

Switching from prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer who have progressed on abiraterone acetate plus prednisone may be beneficial, as suggested by the review of four clinical studies.

Potential candidates for this steroid switch include patients with PSA progression but no clinical or radiological progression, those without severe side effects from CYP-17 inhibition, and individuals unfit for chemotherapy or radium-223.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroid switch after progression on abiraterone acetate plus prednisone. Roviello, G., Sobhani, N., Corona, SP., et al.[2020]

In a study of 95 metastatic castration-resistant prostate cancer (mCRPC) patients, 52% experienced potential drug-drug interactions (DDI) with abiraterone acetate, highlighting the prevalence of polypharmacy in this population.

Patients experiencing pain and those with poorer performance status were found to be at a higher risk for these interactions, suggesting that careful medication reviews by pharmacists are essential to minimize DDI risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential drug-drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: a prevalence study in France. Bonnet, C., Boudou-Rouquette, P., Azoulay-Rutman, E., et al.[2017]

Abiraterone, an irreversible inhibitor of androgen production, significantly improves overall survival in men with metastatic castration-resistant prostate cancer (CRPC), with a median survival of 14.8 months compared to 10.9 months for placebo in patients who had previously undergone chemotherapy.

In chemotherapy-naïve patients, abiraterone also shows a marked increase in radiographic progression-free survival (16.5 months vs. 8.3 months for placebo), although it is associated with manageable side effects like urinary tract infections and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European medicines agency review of abiraterone for the treatment of metastatic castration-resistant prostate cancer in adult men after docetaxel chemotherapy and in chemotherapy-naive disease: summary of the scientific assessment of the committee for medicinal products for human use. Gravanis, I., Lopez, AS., Hemmings, RJ., et al.[2021]

In a study involving 202 patients with metastatic castration-resistant prostate cancer, the sequence of treatment with abiraterone acetate followed by enzalutamide resulted in a longer time to second PSA progression (19.3 months) compared to the reverse sequence (15.2 months), indicating a more effective treatment strategy.

Enzalutamide demonstrated a significantly higher PSA response rate (36%) as a second-line therapy compared to abiraterone (4%), suggesting that enzalutamide is more effective when used after abiraterone in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Khalaf, DJ., Annala, M., Taavitsainen, S., et al.[2021]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

In a study of 53 patients with castration-resistant prostate cancer, both prednisolone and dexamethasone were found to be effective in preventing abiraterone-induced hypokalemia, with no significant changes in serum potassium levels in either group.

Patients receiving dexamethasone had a lower rate of prostate-specific antigen (PSA) elevation and treatment discontinuation compared to those on prednisolone, suggesting that dexamethasone may offer better management of treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consequences of Different Corticosteroids on Serum Potassium and Prostate-Specific Antigen in Patients Receiving Abiraterone for Castration-Resistant Prostate Cancer: A Retrospective Observational Study. Tatsuzawa, M., Ogawa, R., Kinjo, N., et al.[2022]

Citations

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Phase 1/2a study of PRL-02, a long-acting IM depot ... Overall survival following enzalutamide resistance in metastatic castration-sensitive versus metastatic castration-resistant prostate cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04729114

A Safety and Dose-finding Study of PRL-02 Depot in Men ... PRL-02 depot is a potential treatment for men with advanced prostate cancer. It is given by an injection into the muscle. Men with advanced prostate cancer can ...

3. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-prostate-cancer/164044-esmo-2025-phase-1-trial-of-asp5541-prl-02-a-long-acting-intramuscular-depot-injection-of-abiraterone-decanoate-in-patients-with-advanced-prostate-cancer.html

ESMO 2025: Phase 1 Trial of ASP5541 (PRL-02), A Long ... Jose Avitia presented the results of a phase I trial of ASP5541 (PRL-02), a long-acting intramuscular depot injection of abiraterone decanoate in patients with ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT393308

Phase 1/2a study of PRL-02, a long-acting intramuscular ... Phase 1/2a study of PRL-02, a long-acting intramuscular (IM) depot injection of abiraterone decanoate in patients (pts) with advanced prostate cancer.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS5117

Phase 1/2a study of PRL-02, a long-acting intramuscular ... Outcomes of patients (pts) with de novo metastatic hormone-sensitive prostate cancer (mHSPC) who progressed to metastatic castration-resistant ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04729114/

Clinical Trial: NCT04729114 Prostate Adenocarcinoma. Disease States: Advanced - Metastatic, Castration-resistant, Castration-sensitive. Disease Criteria.