Enzalutamide + Relacorilant for Prostate Cancer

Recruiting at 1 trial location

Overseen By Cancer Trials

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Chicago

Must be taking: Androgen deprivation therapy

Must not be taking: Anticonvulsants, Strong CYP3A4 inhibitors

Disqualifiers: Uncontrolled hypertension, Seizure disorder, 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

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers conducting this study hope to learn about the safety and effectiveness of combining two study drugs, relacorilant and enzalutamide, plus androgen deprivation therapy (ADT), also known as hormone therapy. This study is for individuals who have been diagnosed with advanced, high-risk prostate cancer and standard therapies available to treat your disease have not been effective. Participation in this research will last about 3 years and 9 months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any hormonal therapy for prostate cancer or strong inhibitors or inducers of certain liver enzymes due to possible drug interactions. If you are on medications for benign prostate disease, they must be stopped before starting the study.

What data supports the effectiveness of the drug Enzalutamide + Relacorilant for prostate cancer?

Enzalutamide, a component of the treatment, is FDA-approved and has been shown to improve survival in patients with metastatic castration-resistant prostate cancer, suggesting its potential effectiveness in similar conditions. ^{1 2 3 4 5}

Is the combination of Enzalutamide and Relacorilant safe for humans?

Enzalutamide has been studied for safety in patients with prostate cancer, showing it is generally safe but can cause side effects like skin reactions. There is no specific safety data available for Relacorilant in this context. ^{2 3 6 7 8}

What makes the drug Enzalutamide + Relacorilant unique for prostate cancer?

Enzalutamide is a novel drug that blocks the androgen receptor, which is crucial for prostate cancer growth, and is used for castration-resistant prostate cancer. The combination with Relacorilant, which is not detailed in the provided research, suggests a unique approach potentially enhancing the effectiveness of Enzalutamide by targeting additional pathways. ^{2 3 7 9 10}

Research Team

Russell Szmulewitz, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for individuals with advanced, high-risk prostate cancer that hasn't responded to standard treatments. Participants must have confirmed prostatic adenocarcinoma, be surgically resectable, no distant metastases (cancer spread), and an ECOG performance status ≤1 (meaning they are fully active or restricted in physically strenuous activity).

Inclusion Criteria

No evidence of distant metastatic disease on abdominopelvic imaging, bone imaging

Ability to understand and the willingness to sign a written informed consent document

My prostate cancer is confirmed and not small cell type.

Exclusion Criteria

Active psychiatric illness/social situations that would limit compliance with protocol requirements

My blood pressure is high despite taking more than two medications.

I have a history of seizures or I am currently taking seizure medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Participants receive enzalutamide and relacorilant with hormone therapy for neoadjuvant treatment

24 weeks

Surgery

Participants undergo radical prostatectomy after neoadjuvant therapy

Up to 4 weeks post-treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years and 9 months

Treatment Details

Interventions

• Enzalutamide
• Relacorilant

Trial Overview The study tests combining relacorilant and enzalutamide with hormone therapy against a placebo plus hormone therapy in treating high-risk localized prostate cancer. The goal is to assess the safety and effectiveness of this combination over approximately 3 years and 9 months.

Participant Groups

Group I: Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide Experimental Treatment 4 Interventions

All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/relacorilant with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).

Group II: Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide Experimental Treatment 4 Interventions

All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/placebo (sugar pill in the form of 2 softgel capsules) with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).

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 Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., 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]

Enzalutamide, a treatment for metastatic castration-resistant prostate cancer, was linked to a case of acute generalized exanthematous pustulosis (AGEP) in a 62-year-old male patient, indicating a potential skin-related side effect of this medication.

The patient's skin reaction occurred shortly after starting enzalutamide and resolved within four weeks, suggesting that the long half-life of enzalutamide (5.8 days) may contribute to the prolonged duration of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. Alberto, C., Konstantinou, MP., Martinage, C., et al.[2020]

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]

Enzalutamide (Enz) was evaluated in a retrospective study of 47 men with heavily pretreated metastasized castration-resistant prostate cancer (mCRPC), showing a 23% response rate with significant PSA declines, indicating its potential efficacy even in later treatment lines.

The treatment was generally well tolerated, with common side effects like fatigue and nausea, and resulted in a median overall survival of 40.1 weeks and a median progression-free survival of 12.1 weeks, suggesting it can be a viable option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide as a Fourth- or Fifth-Line Treatment Option for Metastatic Castration-Resistant Prostate Cancer. Badrising, SK., van der Noort, V., Hamberg, P., et al.[2021]

In a study involving 507 patients with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide was found to be well tolerated, with 88.2% of patients experiencing adverse events (AEs), primarily mild to moderate in severity.

The safety profile of enzalutamide in this expanded access program was consistent with previous studies, with fatigue, nausea, and anorexia being the most common side effects, and only a small percentage (0.8%) experiencing seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel: expanded access in North America. Joshua, AM., Shore, ND., Saad, F., et al.[2021]

Enzalutamide effectively inhibits androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) by blocking multiple steps, including androgen binding and nuclear translocation, without exhibiting AR agonistic activity, which is a significant advantage over bicalutamide.

In preclinical models, enzalutamide not only reduced tumor volume in CRPC xenografts but also induced apoptosis in prostate cancer cells, suggesting its potential as a powerful treatment option for patients with advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer. Guerrero, J., Alfaro, IE., Gómez, F., et al.[2022]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

Oral enzalutamide (Xtandi®) is an effective treatment for castration-resistant prostate cancer (CRPC), showing efficacy in both nonmetastatic and metastatic cases, as well as in patients who have or have not undergone chemotherapy.

Enzalutamide is generally well tolerated and is particularly beneficial for high-risk nonmetastatic CRPC patients, making it a key first-line treatment option for those with metastatic CRPC, regardless of their chemotherapy history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: A Review in Castration-Resistant Prostate Cancer. Scott, LJ.[2021]

In a phase III study involving men with progressive castration-resistant prostate cancer, enzalutamide significantly improved overall survival compared to placebo, with a median survival of 18.4 months versus 13.6 months.

Enzalutamide also showed benefits across all secondary endpoints, including a higher rate of prostate-specific antigen (PSA) decline and improved quality of life, although it was associated with common side effects like fatigue and diarrhea, and a rare incidence of seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer. Hoffman-Censits, J., Kelly, WK.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. [2022]

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

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

3. Poland pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. [2020]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Enzalutamide as a Fourth- or Fifth-Line Treatment Option for Metastatic Castration-Resistant Prostate Cancer. [2021]

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

Safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel: expanded access in North America. [2021]

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

Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

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

Enzalutamide: A Review in Castration-Resistant Prostate Cancer. [2021]

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

Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer. [2021]