EPI-7386 + Enzalutamide for Prostate Cancer

Recruiting at 1 trial location

Overseen By Pedro Barata, MD, MSc

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Pedro Barata, MD, MSc

Must be taking: LHRH agonist/antagonist

Must not be taking: CYP3A inducers, CYP2C8 inhibitors

Disqualifiers: mCRPC, Seizure history, Other malignancy, 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: 3

Duration: 36 months

13 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to study the effects of EPI-7386 in combination with Enzalutamide on participants diagnosed with prostate cancer. The main goals of this study are to evaluate the antitumor activity of EPI-7386 in combination with enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC), and to evaluate the pharmacokinetics (PK) of EPI-7386 when dosed in combination with enzalutamide. Participants will will take the study drug, EPI-7360, twice a day by mouth and enzalutamide once a day by mouth, alongside clinic visits every two weeks.

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 use certain drugs that affect liver enzymes (CYP3A and CYP2C8) before starting the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research shows that Enzalutamide, a drug used for prostate cancer, significantly improves survival rates and delays disease progression in men with castration-resistant prostate cancer. It has been shown to increase survival by several months and is well tolerated by patients. ^{1 2 3 4 5}

What safety information is available for the treatment EPI-7386 + Enzalutamide for prostate cancer?

Enzalutamide, used for prostate cancer, is generally well tolerated but can cause side effects like fatigue, diarrhea, back pain, hot flashes, and high blood pressure. Rarely, it may lead to seizures or breast-related issues. Safety data for EPI-7386 is not provided in the available research. ^{1 3 4 6 7}

What makes the drug EPI-7386 + Enzalutamide unique for prostate cancer?

The combination of EPI-7386 and Enzalutamide is unique because it targets the androgen receptor signaling pathway, which is crucial in the progression of castration-resistant prostate cancer (CRPC). Enzalutamide is an oral drug that blocks the androgen receptor's interaction with DNA, helping to slow down cancer growth and improve survival rates in patients who have already undergone chemotherapy. ^{1 2 3 8 9}

Research Team

Pedro Barata, MD, MSc

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Christopher Wee, MD

Principal Investigator

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for individuals with newly diagnosed metastatic hormone-sensitive prostate cancer. Participants will take EPI-7386 and Enzalutamide orally, alongside standard Androgen Deprivation Therapy. They must be able to attend clinic visits every two weeks.

Inclusion Criteria

My blood tests show normal organ function and healthy blood cell counts.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <5 × ULN at screening

My prostate cancer is confirmed and does not have small cell or neuroendocrine features.

Exclusion Criteria

Receipt of any other investigational agents

I am not taking medications that are highly affected by other drugs.

I have had surgery on my stomach that affects how I absorb food or medicine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive EPI-7386 and Enzalutamide orally for 36 months

36 months

Clinic visits every two weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Enzalutamide
• EPI-7386

Trial Overview The study tests the effectiveness of a new drug combination: EPI-7386 with Enzalutamide, in addition to standard Androgen Deprivation Therapy, against prostate cancer. It aims to assess tumor response and understand how the body processes these drugs.

Participant Groups

Group I: EPI-7386 + Enzalutamide Experimental Treatment 3 Interventions

EPI-7386 at 600 mg twice daily orally with standard of care Enzalutamide at 160 mg, once daily, orally for 36 months of treatment (11 cycles).

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?

Pedro Barata, MD, MSc

Lead Sponsor

Trials

1

Recruited

10+

ESSA Pharma Inc.

Collaborator

Trials

1

Recruited

10+

Findings from Research

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 (XTANDI) is an FDA-approved treatment for castration-resistant prostate cancer (CRPC) that effectively targets androgen receptor signaling, which is crucial for cancer progression.

In a Phase III clinical trial involving men with CRPC after chemotherapy, enzalutamide was well tolerated and significantly improved overall survival by 4.8 months, as indicated by reduced serum prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. Dhingra, R., Sharma, T., Singh, S., et al.[2021]

In the PREVAIL trial, enzalutamide significantly improved both radiographic progression-free survival and overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (CRPC), demonstrating its efficacy as a treatment option.

Enzalutamide was well tolerated and delayed the need for chemotherapy and decline in health-related quality of life, making it a convenient choice for patients who are asymptomatic or mildly symptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer. Keating, GM.[2021]

In a phase 3 trial involving 1401 men with nonmetastatic, castration-resistant prostate cancer, enzalutamide significantly improved median overall survival to 67.0 months compared to 56.3 months for placebo, indicating a 27% lower risk of death.

The safety profile of enzalutamide was consistent with previous studies, with a similar rate of serious adverse events compared to placebo, primarily involving fatigue and musculoskeletal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. Sternberg, CN., Fizazi, K., Saad, F., et al.[2021]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

Enzalutamide significantly improves survival and delays skeletal-related events in patients with metastatic castration-resistant prostate cancer (mCRPC), as shown in the phase III AFFIRM study with consistent benefits across all subgroups.

In the phase III PREVAIL study, enzalutamide reduced the risk of radiographic progression and death in chemotherapy-naïve mCRPC patients, while also demonstrating a favorable safety profile with similar adverse event rates compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on enzalutamide in the treatment of prostate cancer. Merseburger, AS., Haas, GP., von Klot, CA.[2020]

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]

In a phase III trial involving patients with metastatic, castration-resistant prostate cancer (mCRPC) who had progressed after docetaxel treatment, enzalutamide significantly improved overall survival, with a median survival of 18.4 months compared to 13.6 months for placebo, indicating a 37% reduction in mortality risk.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although there is a small, dose-dependent risk of seizures; it also improved quality of life and pain management for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. Sanford, M.[2021]

References

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

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

2. Poland pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. [2021]

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

Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer. [2021]

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

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

An update on enzalutamide in the treatment of prostate cancer. [2020]

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

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

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

Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. [2021]