Enzalutamide +/- Radium Ra 223 for Prostate Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the drug enzalutamide (also known as Xtandi), with or without an additional treatment called radium Ra 223, for prostate cancer that has spread and resists hormone therapy. Enzalutamide blocks male hormones that promote cancer growth, while radium Ra 223 uses radiation to kill cancer cells. Men with prostate cancer affecting their bones, even without symptoms, and who haven't undergone certain types of chemotherapy, might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

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

Research has shown that enzalutamide is generally well-tolerated by patients with prostate cancer. In studies, it reduced the risk of death by 33% compared to a group not receiving the treatment, demonstrating its effectiveness and safety for most people. Patients taking enzalutamide had higher survival rates than those on other treatments, making it a reliable option.

For the combination of enzalutamide and radium Ra 223, less direct information is available. However, since enzalutamide is already approved for prostate cancer, this offers some reassurance about its safety. The current phase of the trial suggests that the treatment showed promise in earlier research, indicating it is likely well-tolerated, but more studies are needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine enzalutamide, a medication that blocks the effects of androgens (hormones that can promote prostate cancer growth), with radium Ra 223, a radioactive substance that targets cancer in the bones, where prostate cancer often spreads. This combination offers a two-pronged attack: enzalutamide disrupts cancer cell growth at its source, while radium Ra 223 delivers targeted radiation therapy to bone metastases. This dual approach could potentially enhance the effectiveness of treatment compared to using enzalutamide alone or other standard therapies like chemotherapy.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that enzalutamide, one of the treatments in this trial, effectively treats prostate cancer. One study found that 50% of patients taking enzalutamide were still alive after 96 months, compared to 40% of those on other treatments. Enzalutamide also reduced the risk of cancer progression by 60%, leading to better patient outcomes.

In this trial, some participants will receive enzalutamide alone, while others will receive a combination of enzalutamide and Radium Ra 223 dichloride. Radium Ra 223 dichloride, when combined with enzalutamide, targets cancer cells with powerful particles. This approach has been shown to kill cancer cells, helping to shrink tumors and slow cancer spread. Together, enzalutamide and Radium Ra 223 may more effectively stop cancer growth in patients with advanced prostate cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

David I Quinn, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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 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]

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. targetedonc.com targetedonc.com/shorts/a-13-year-old-drug-s-persisting-power-in-prostate-cancer

A 13-Year-Old Drug's Persisting Power in Prostate Cancer Two-year OS rates were 80% vs 63%. The treatment also yielded a record 57.1% pathological pCR. ... Clinical Trial Achieves 60% Reduction in the Risk of Tumor ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510310?query=featured_home

Improved Survival with Enzalutamide in Biochemically ... In this trial, enzalutamide plus leuprolide led to significantly longer overall survival than leuprolide alone among patients with castration- ...

4. 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 ...

5. 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 ...

6. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-reduced-risk-death-40-vs-leuprolide

XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ... The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12504157/

Comparative effectiveness and safety of enzalutamide ... Enzalutamide use was associated with superior overall survival (hazard ratio 0.88, 95% confidence interval [CI] 0.82–0.96) compared with ...

8. xtandi.com xtandi.com/clinical-trials

Clinical Trial Results | XTANDI® (enzalutamide) Men taking XTANDI had a 61% lower chance of their cancer progressing compared with men not taking XTANDI during the study. Progression was seen in 89 men (15.5 ...