What side effects are associated with this type of intervention?

Common treatments for prostate cancer, particularly androgen receptor antagonists and inhibitors like EPI-7386 and enzalutamide, are associated with side effects such as fatigue, anorexia, nausea, and an increased risk of seizures. When combined with other treatments like docetaxel, enzalutamide can lead to higher toxicity. These treatments may also cause gastrointestinal issues and central nervous system effects.

What prior FDA approvals exist?

The FDA has approved several androgen receptor inhibitors for the treatment of prostate cancer, including enzalutamide, apalutamide, and darolutamide. Enzalutamide, approved for both metastatic and nonmetastatic castration-resistant prostate cancer (CRPC), works by inhibiting multiple steps in the androgen receptor signaling pathway. Apalutamide, similar in mechanism to enzalutamide, is approved for nonmetastatic CRPC and metastatic castration-sensitive prostate cancer (CSPC). Darolutamide, another androgen receptor antagonist, is approved for nonmetastatic CRPC and is noted for its lower central nervous system toxicity. These drugs are part of the modern therapeutic approach targeting androgen receptor pathways in prostate cancer treatment.

What other types of research exist?

Promising alternatives to EPI-7386 and enzalutamide for prostate cancer treatment in 2024 include: 1) Darolutamide, which has shown efficacy in delaying growth of enzalutamide-resistant prostate cancer, particularly in cells with mutated androgen receptors. 2) The combination of androgen deprivation therapy (ADT) with docetaxel and either darolutamide or abiraterone, which significantly improves overall survival in high-risk/high-volume metastatic disease. 3) Bipolar androgen therapy (BAT), which involves cyclical high-dose testosterone therapy and has shown potential in resensitizing CRPC to further androgen-directed therapies.

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Androgen Receptor Antagonist

EPI-7386 + Enzalutamide for Prostate Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by ESSA Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Evidence of castration-resistant prostate cancer (CRPC)

Males ≥18 years

Must not have

Significant cardiovascular disease

Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and CYP2B6

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to end of cycle 1 (each cycle is 28 days)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, EPI-7386, taken by mouth along with an existing drug, enzalutamide, in patients with advanced prostate cancer that hasn't responded to standard treatments. Both drugs work together to block signals that make cancer cells grow.

Who is the study for?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, who haven't used second-generation anti-androgens or certain other treatments recently. They must have good performance status (able to carry out daily activities) and organ function, with low testosterone levels maintained by ongoing treatment.

What is being tested?

The trial is testing a new drug combo for advanced prostate cancer. Phase 1 checks the safety of EPI-7386 with enzalutamide at different doses. Phase 2 compares two groups: one taking both drugs and another taking only enzalutamide, based on earlier results for effectiveness without worsening disease.

What are the potential side effects?

Possible side effects include typical reactions from cancer medications such as fatigue, digestive issues, skin reactions, potential blood disorders, hormonal changes affecting mood or energy levels, and possibly seizures due to the nature of these drugs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My prostate cancer is not responding to hormone therapy.

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I am a man aged 18 or older.

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I am fully active or can carry out light work.

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I have not taken second generation anti-androgens.

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My cancer has spread to my bones or other parts of my body, confirmed by scans.

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My prostate cancer has been confirmed by a lab test.

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I am on hormone therapy for cancer or have had surgery to remove my testicles.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious heart condition.

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I am not taking medication that is sensitive to certain liver enzymes.

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I have spinal cord compression.

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I cannot be treated with enzalutamide.

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I have a rare hereditary fructose intolerance.

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My brain metastasis has been treated and stable for at least 28 days.

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I am not taking medications that strongly affect liver enzyme CYP2C8.

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I am allergic to ingredients in EPI-7386 or enzalutamide.

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I am not taking medication that strongly affects liver enzymes.

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I haven't used hormonal agents for prostate cancer in the last 28 days.

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I had targeted bone radiotherapy or any radiotherapy within the last 2 weeks.

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I have stomach or intestine problems that affect how my body absorbs medicine.

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I haven't used any immune system boosters in the last week.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to end of cycle 1 (each cycle is 28 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to end of cycle 1 (each cycle is 28 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to end of cycle 1 (each cycle is 28 days) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: Incidence of Dose Limiting Toxicities

Phase 1: Incidence of laboratory abnormalities as a measure of safety and tolerability of EPI-7386

Phase 1: Incidence of treatment emergent adverse events

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Active Control

Group I: Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1)Experimental Treatment1 Intervention

RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg

Group II: Phase 1 Cohort 4Experimental Treatment1 Intervention

RP2D mg EPI-7386 in combination of Enzalutamide160 mg

Group III: Phase 1 Cohort 3Experimental Treatment1 Intervention

600 mg BID EPI-7386 in combination of Enzalutamide120 mg

Group IV: Phase 1 Cohort 2Experimental Treatment1 Intervention

800 mg QD EPI-7386 in combination of Enzalutamide120 mg

Group V: Phase 1 Cohort 1Experimental Treatment1 Intervention

600 mg QD EPI-7386 in combination of Enzalutamide120 mg

Group VI: Phase 2 Enzalutamide single agentActive Control1 Intervention

Enzalutamide 160 mg

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target the androgen receptor (AR) pathway, which is crucial for the growth and survival of prostate cancer cells. Androgen receptor antagonists, like EPI-7386, block the binding of androgens (male hormones) to the AR, preventing the activation of the receptor. Androgen receptor inhibitors, such as enzalutamide, not only block androgen binding but also inhibit the AR's nuclear translocation and its interaction with DNA, further disrupting cancer cell growth. These mechanisms are vital for prostate cancer patients because they effectively reduce the cancer's ability to use androgens for growth, thereby slowing disease progression and improving survival outcomes.

Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.Androgen Deprivation Therapy and Secondary Hormone Therapy in the Management of Hormone-sensitive and Castration-resistant Prostate Cancer.