Enzalutamide + Radium 223 for Metastatic Prostate Cancer

(PEACE III Trial)

Recruiting at 63 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

446 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of the trial is to assess if upfront combination of enzalutamide and Ra223 improves radiological progression-free survival (rPFS1) compared to enzalutamide single agent in CRPC patients metastatic to bone

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.

What data supports the effectiveness of the drug combination of Enzalutamide and Radium-223 for metastatic prostate cancer?

Research shows that both Radium-223 and Enzalutamide, when used separately, have been effective in improving survival in patients with metastatic castration-resistant prostate cancer. Combining these drugs is of interest because they work in different ways and have non-overlapping side effects, which may lead to better outcomes. ^{1 2 3 4 5}

Is the combination of Enzalutamide and Radium-223 safe for humans?

Studies have looked at the safety of using Enzalutamide and Radium-223 together for prostate cancer. They have different ways of working and don't have overlapping side effects, but there is limited information on their combined safety, especially regarding blood-related side effects. ^{3 4 5 6 7}

How is the drug combination of Enzalutamide and Radium-223 unique for treating metastatic prostate cancer?

The combination of Enzalutamide and Radium-223 is unique because it uses two different mechanisms to target cancer: Enzalutamide blocks male hormones that fuel cancer growth, while Radium-223 delivers targeted radiation to bone metastases. This combination aims to improve outcomes by leveraging their non-overlapping side effects and enhanced antitumor efficacy. ^{2 3 4 5 8}

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

Eligibility Criteria

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.

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

I am currently on hormone therapy for cancer.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. United States 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. [2021]

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

Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies. [2021]

4. United States 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. [2021]

5. England 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. [2022]

6. United States 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. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Enhanced Antitumor Efficacy of Radium-223 and Enzalutamide in the Intratibial LNCaP Prostate Cancer Model. [2023]