Enzalutamide +/- Radium Ra 223 for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Cheryl Kefauver, RN

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Southern California

Must be taking: LHRH therapy

Must not be taking: Docetaxel, Cabazitaxel, Enzalutamide, Corticosteroids

Disqualifiers: Seizures, CNS metastases, Hepatitis, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 24 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies how well enzalutamide with or without radium Ra 223 dichloride in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Enzalutamide is an androgen receptor inhibitor that may slow down the growth of prostate cancer by blocking the action of the male hormone testosterone and other male hormones called androgens. Radiation therapy uses high energy alpha particles to kill tumor cells and shrink tumors. Enzalutamide with or without radium Ra 223 dichloride may work better in treating patients with castration-resistant prostate cancer.

Will I have to stop taking my current medications?

The trial requires a 2-week period without taking certain medications like bicalutamide, flutamide, nilutamide, abiraterone, ketoconazole, or estrogen before starting enzalutamide. If you're on oral corticosteroids or other immunosuppressive agents, you may need to stop those as well, unless they're for adrenal replacement. Topical or inhaled steroids are allowed.

What data supports the effectiveness of the drug Enzalutamide +/- Radium Ra 223 for prostate cancer?

Research shows that Radium-223 and Enzalutamide, when used separately, have improved survival in patients with metastatic castration-resistant prostate cancer. Combining these drugs is of interest because they work differently and have non-overlapping side effects, suggesting potential benefits when used together. ^{1 2 3 4 5}

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

The combination of Enzalutamide and Radium Ra 223 has been studied for safety in patients with prostate cancer, and long-term safety has been confirmed in clinical trials. However, there are reports of hematologic toxicity (blood-related side effects) when these treatments are used together. ^{2 4 6 7 8}

How is the drug Enzalutamide combined with Radium Ra 223 unique for prostate cancer treatment?

The combination of Enzalutamide and Radium Ra 223 is unique because it uses two different approaches to treat prostate cancer: Enzalutamide blocks male hormones that fuel cancer growth, while Radium Ra 223 targets and kills cancer cells in the bones. This combination aims to improve outcomes by using their differing actions and minimizing overlapping side effects. ^{1 2 3 4 5}

Research Team

David I Quinn, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for men with metastatic, castration-resistant prostate cancer that has spread to the bone. Participants must have a hemoglobin level of at least 9.5 g/dL, rising PSA levels, and be in good physical condition (ECOG status 0-1). They should not have had certain prior treatments like docetaxel or cabazitaxel for metastatic cancer and no recent seizures or significant cardiovascular events.

Inclusion Criteria

Platelets >= 100,000

Total bilirubin within normal institutional limits

Hemoglobin >= 9.5 g/dL

Exclusion Criteria

I am not taking oral steroids or immunosuppressants, except for adrenal replacement.

I do not have untreated brain metastases or leptomeningeal disease.

I have hepatitis B, C, or cirrhosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enzalutamide daily and radium Ra 223 dichloride every 28 days for up to 6 courses

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Every 3 months

Treatment Details

Interventions

• Enzalutamide
• Radium Ra 223 Dichloride

Trial Overview The study is testing whether enzalutamide alone or combined with radium Ra 223 dichloride is more effective in treating prostate cancer that resists standard hormone therapy. Enzalutamide blocks male hormones to slow cancer growth; radium Ra 223 delivers radiation directly to tumors.

Participant Groups

Group I: Arm II (enzalutamide) Experimental Treatment 2 Interventions

Patients receive enzalutamide as in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (enzalutamide, radium 223) Experimental Treatment 3 Interventions

Patients receive enzalutamide PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive radium Ra 223 dichloride IV on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 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 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]

The combination of radium-223 and enzalutamide was confirmed to be safe over a median follow-up of 22 months, with no increase in fractures or adverse events compared to enzalutamide alone.

Patients receiving the combination treatment experienced a significant improvement in prostate-specific antigen progression-free survival (PSA-PFS2), suggesting enhanced efficacy in managing metastatic castration-resistant prostate cancer (mCRPC).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 plus Enzalutamide Versus Enzalutamide in Metastatic Castration-Refractory Prostate Cancer: Final Safety and Efficacy Results. Maughan, BL., Kessel, A., McFarland, TR., et al.[2022]

References

1. 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]

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

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

3. 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]

4. 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]

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

Results From a Large, Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region. [2019]

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. England pubmed.ncbi.nlm.nih.gov

Radium-223 plus Enzalutamide Versus Enzalutamide in Metastatic Castration-Refractory Prostate Cancer: Final Safety and Efficacy Results. [2022]