Enzalutamide + Radium 223 for Metastatic Prostate Cancer

(PEACE III Trial)

Not currently recruiting at 67 trial locations

Overseen By EORTC

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Must be taking: Bone protecting agents

Must not be taking: Cyp17 inhibitors, Ketoconazole

Disqualifiers: Cardiovascular disease, Seizure history, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 223

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two treatments, enzalutamide (a hormone therapy) and Ra223 (a radiopharmaceutical), can slow the spread of prostate cancer to the bones more effectively than enzalutamide alone. It targets men whose prostate cancer has become resistant to hormone therapy and has spread to their bones. Participants should have at least four bone metastases with little to no pain and no cancer spread to organs like the liver or lungs. The study explores whether the combination treatment extends the time patients live without cancer progression. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but certain medications are not allowed, such as Cyp17 inhibitors and ketoconazole. You should discuss your current medications with the trial team to see if any need to be adjusted or stopped.

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

Previous studies have shown enzalutamide to be safe for treating prostate cancer. A large study with over 2,000 patients found that enzalutamide lowered the risk of death and was generally well-tolerated. Common side effects included tiredness and hot flashes, which most patients managed.

Research on Ra223 (radium-223) also shows it is safe for men with prostate cancer that has spread to the bones. Patients who received several doses of Ra223 lived longer. The treatment was generally well-tolerated, although some patients experienced a decrease in blood cell production, a known risk.

Both treatments have undergone extensive study, demonstrating their safe use with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for metastatic prostate cancer, which often include hormone therapies and chemotherapy, the combination of Enzalutamide and Radium 223 offers a unique approach by integrating a powerful hormonal therapy with a targeted radiopharmaceutical. Enzalutamide works by blocking the effects of androgens (male hormones) that can promote cancer growth, while Radium 223 specifically targets bone metastases, delivering radiation directly to the cancer cells in the bones. This dual approach not only aims to control the spread of cancer but also addresses bone-related complications, which are common in advanced prostate cancer. Researchers are excited because this combination has the potential to improve outcomes by tackling the disease on multiple fronts.

What evidence suggests that the combination of enzalutamide and Ra223 might be an effective treatment for metastatic prostate cancer?

Studies have shown that enzalutamide, one of the treatments in this trial, effectively treats prostate cancer that has spread to other parts of the body. It can reduce the risk of death by 33% compared to other treatments and helps patients live longer without their cancer worsening. In this trial, some participants will receive enzalutamide alone. Research also indicates that using Ra223 early and in multiple cycles can extend life and delay bone problems in men with this cancer. Another group in this trial will receive a combination of enzalutamide and Ra223. Together, these treatments aim to slow the disease and improve patients' quality of life. ^{1 2 3 4 6}

Who Is on the Research Team?

Bertrand Tombal, Prof

Principal Investigator

Cliniques Universitaires de Saint Luc

Silke Gillessen, Prof

Principal Investigator

Oncology Institute of Southern Switzerland - Ospedale San Giovanni

Are You a Good Fit for This Trial?

Men at least 18 years old with prostate cancer that has spread to the bones and are asymptomatic or mildly symptomatic. They must have stopped certain treatments like abiraterone four weeks prior, not had other specific cancer treatments, no seizures in the past year, and be able to comply with study requirements. Those with serious health issues or conditions affecting study participation are excluded.

Inclusion Criteria

My prostate cancer was confirmed through a tissue examination.

I am currently on hormone therapy for cancer.

My cancer has spread to my bones with 4 or more spots.

Exclusion Criteria

I have not had certain treatments that are not allowed in this trial.

My cancer has not spread to my brain or spinal cord.

I am not taking narcotic painkillers for bone pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enzalutamide daily and Ra223 monthly for 6 months

6 months

Monthly visits for Ra223 administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

46 months

Long-term follow-up

Participants are monitored for overall survival and other secondary outcomes

63 months

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Ra223

Trial Overview The trial is testing if combining enzalutamide (a hormone therapy) and Ra223 (a radioactive drug) improves survival without cancer progression compared to just enzalutamide alone in men whose prostate cancer has spread to their bones.

How Is the Trial Designed?

Group I: Enzalutamide and Ra223 Experimental Treatment 2 Interventions

Ra223 will be administered 55kBq/kg standard dose monthly for 6 months and given in combination with enzalutamide at a dose of 160 mg daily.

Group II: Enzalutamide Active Control 1 Intervention

Enzalutamide will be given at a dose of 160 mg daily

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

European Organisation for Research and Treatment of Cancer - EORTC

Lead Sponsor

Trials

417

Recruited

166,000+

Latin American Cooperative Oncology Group

Collaborator

Trials

43

Recruited

15,600+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Cancer Trials Ireland

Collaborator

Trials

85

Recruited

25,600+

Astellas Pharma Europe Ltd.

Industry Sponsor

Trials

34

Recruited

77,500+

UNICANCER

Collaborator

Trials

237

Recruited

352,000+

Canadian Urologic Oncology Group

Collaborator

Trials

8

Recruited

920+

Published Research Related to This Trial

Radium-223, when used concurrently with next-generation antiandrogen therapies like enzalutamide or abiraterone, shows similar hematologic toxicity levels to those seen with Radium-223 alone, indicating it is well tolerated in patients with advanced prostate cancer.

In a study of 25 patients, no significant differences in blood counts were observed between those receiving Radium-223 alone and those receiving it with antiandrogens, suggesting that combining these treatments does not increase the risk of severe blood-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies. Dan, TD., Eldredge-Hindy, HB., Hoffman-Censits, J., et al.[2021]

In a study of 51 patients with bone-dominant metastatic castration-resistant prostate cancer (mCRPC), the combination of enzalutamide with radium-223 (Ra-223) did not show a significant improvement in overall survival compared to Ra-223 alone, with median survival times of 20.4 months and 17.5 months, respectively.

The only factors associated with improved overall survival were a pre-treatment PSA level of less than 30 ng/mL and a performance status of less than 2, indicating that these may be important predictors for better outcomes in patients receiving Ra-223.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 in the Third-Line Setting in Metastatic Castration-Resistant Prostate Cancer: Impact of Concomitant Use of Enzalutamide on Overall Survival (OS) and Predictors of Improved OS. Ahmed, ME., Joshi, VB., Badawy, M., et al.[2021]

The combination of enzalutamide and radium 223 (Ra 223) in treating metastatic castration-resistant prostate cancer (CRPC) was found to be safe and tolerable, with 87% of participants completing all treatment cycles without unexpected toxicities.

Patients reported improvements in quality of life and pain management, and there were no significant increases in serious adverse events, falls, or deaths, suggesting that this combination therapy could be beneficial for managing CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open Label Phase II Study of Enzalutamide With Concurrent Administration of Radium 223 Dichloride in Patients With Castration-Resistant Prostate Cancer. Shore, ND., Schellhammer, PF., Tutrone, RF., et al.[2021]

In a phase II study of 45 patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of radium-223 and enzalutamide was found to be tolerable, with 93.3% of patients completing all six cycles of treatment.

While the combination treatment had a low incidence of fractures during therapy, a notable number of patients (37.8%) experienced fractures at any time during the study, particularly after completing the combination, highlighting the need for monitoring bone health during and after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 in combination with enzalutamide in metastatic castration-resistant prostate cancer: a multi-centre, phase II open-label study. McDermott, RS., Greene, J., McCaffrey, J., et al.[2022]

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

In a study of 60 patients with metastatic castration-resistant prostate cancer, combining radium-223 with either abiraterone or enzalutamide did not improve overall survival compared to radium-223 alone, with median survival times of 12.7 and 12.8 months respectively.

However, the combination treatment did significantly extend progression-free survival (7.6 months vs. 4.9 months), without increasing the risk of serious adverse events, suggesting a potential benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer. Kim, SI., Szeto, AH., Morgan, KP., et al.[2021]

In a study of 228 men with metastatic castration-resistant prostate cancer treated with radium 223 (Ra-223), the median overall survival was 11.1 months, with chemotherapy-naïve patients showing better survival (12.3 months) compared to those who had prior chemotherapy (8.1 months).

Ra-223 treatment improved pain scores in 54% of patients and overall quality of life, although the fracture rate was notably high (24%) in patients previously treated with abiraterone and prednisolone, suggesting the need for routine bone health evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimising Radium 223 Therapy for Metastatic Castration-Resistant Prostate Cancer -5-year Real-World Outcome: Focusing on Treatment Sequence and Quality of Life. Jiang, XY., Atkinson, S., Pearson, R., et al.[2021]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/astellas-and-pfizers-xtanditm-enzalutamide-shows-long-term

Astellas and Pfizer's XTANDI™ (enzalutamide) Shows ... OS at 96 months was 50% with XTANDI and 40% for NSAA; progression-free survival (PFS) also favored XTANDI over NSAA (HR: 0.49; 95% CI, 0.42-0.57) ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40660075/

The efficacy and safety of enzalutamide in metastatic ... Results: The data of 2275 patients were analyzed eventually. Enzalutamide reduced the risk of death by 33% compared to the control. Specifically ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303974

Improved Outcomes with Enzalutamide in Biochemically ... After a median follow-up of 60.7 months, enzalutamide plus leuprolide and enzalutamide monotherapy significantly improved metastasis-free ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833622

Enzalutamide and Prostate-Specific Antigen Levels in ... In this study, enzalutamide plus ADT was associated with improved outcomes in men with mHSPC regardless of pretreatment PSA level.

5. xtandihcp.com xtandihcp.com/cspc/efficacy

Efficacy CSPC | HCP Site | XTANDI® (enzalutamide) XTANDI (single agent) significantly improved metastasis-free survival vs placebo + GnRH therapy* · Number of events: 63 (17.7%) with XTANDI (single agent) vs 92 ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0302283820303298

Five-year Survival Prediction and Safety Outcomes with ... At the 5-yr data cutoff, 1382 of 1717 (80%) men had died. Enzalutamide reduced the hazard of death by 17% (hazard ratio 0.83; 95% confidence interval [CI] ...