Enzalutamide + Relacorilant for Prostate Cancer

Overseen By Cancer Clinical Trials Office

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Chicago

Must not be taking: Hormonal therapy, Corticosteroids

Disqualifiers: Visceral disease, Seizure disorder, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

35 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is an open-label Phase 1 study of the combination of relacorilant with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC).

Will I have to stop taking my current medications?

The trial requires stopping certain medications, like hormonal therapies and systemic corticosteroids, at least 2 weeks before starting the study drug. If you're on strong inhibitors or inducers of specific enzymes (CYP3A4 or CYP2C8), you may also need to stop those due to possible drug interactions.

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

Research shows that Enzalutamide is effective for treating metastatic castration-resistant prostate cancer, improving survival rates in patients who have already undergone other treatments. ^{1 2 3 4 5}

Is the combination of Enzalutamide and Relacorilant safe for humans?

Enzalutamide, used for prostate cancer, has been studied for safety and is generally considered safe, but it can cause side effects like skin reactions and other toxicities. There is no specific safety data available for the combination with Relacorilant. ^{3 4 6 7 8}

How is the drug combination of Enzalutamide and Relacorilant unique for treating prostate cancer?

The combination of Enzalutamide and Relacorilant is unique because Enzalutamide is a potent androgen receptor inhibitor that blocks multiple steps in the signaling pathway crucial for prostate cancer growth, while Relacorilant is being explored for its potential to enhance the effectiveness of cancer treatments, making this combination a novel approach compared to standard treatments. ^{2 3 4 8 9}

Research Team

Russell Szmulewitz, MD

Principal Investigator

University of Chicago

Eligibility Criteria

Men with advanced prostate cancer that has resisted castration and shown progression despite previous treatments, but not including prior GR antagonist therapy. Participants must have stable vital functions, no history of seizures or certain other medical conditions, and agree to use two forms of birth control if applicable.

Inclusion Criteria

My prostate cancer has spread and this was confirmed through testing.

My testosterone levels are very low or I've had surgery to lower them.

I have been treated with medications like abiraterone for prostate cancer.

Exclusion Criteria

I have been able to stop taking steroids after using them for more than 3 months.

My scans show internal organ cancer, and I can undergo strong chemotherapy.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive relacorilant and enzalutamide daily with dose adjustments based on safety and pharmacokinetics

28 days

Regular visits for safety and PK assessments

Dose Expansion

Cohort expanded to 12 patients to refine safety and PK at the recommended phase II dose

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Enzalutamide
• Relacorilant

Trial Overview The trial is testing a combination of Enzalutamide and Relacorilant in men with metastatic castration-resistant prostate cancer (mCRPC). It's an early-phase study where both drugs are given openly to see how well they work together.

Participant Groups

Group I: Dose Level Experimental Treatment 2 Interventions

Relacorilant will be given at a dose once daily. Enzalutamide will be given at a dose once 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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Corcept Therapeutics

Industry Sponsor

Trials

72

Recruited

7,700+

Dr. Joseph K. Belanoff

Corcept Therapeutics

Chief Executive Officer since 2014

MD from Stanford University

Dr. William Guyer

Corcept Therapeutics

Chief Medical Officer since 2021

PharmD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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 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]

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 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]

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]

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]

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. 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]

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

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

4. Poland pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. Germany pubmed.ncbi.nlm.nih.gov

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

7. 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]

8. 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]

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

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