EPI-7386 + Enzalutamide for Prostate Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, EPI-7386 and Enzalutamide (also known as Xtandi), to evaluate their effectiveness in treating prostate cancer that has spread and still responds to hormone therapy. The researchers aim to understand how well this combination fights cancer and how the body processes these drugs. Men with prostate cancer that has spread and who have not used certain advanced hormone treatments might be suitable for this study. Participants will take the study drugs orally and attend clinic visits every two weeks. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the combination of EPI-7386 and Enzalutamide is generally well-tolerated, causing few serious side effects. Participants in previous studies experienced good safety outcomes with this treatment. It has also effectively blocked the androgen receptor pathway, crucial for treating prostate cancer. Although some side effects occurred, most were manageable and did not necessitate stopping the treatment. This is encouraging for those considering joining a trial with this combination therapy. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about the combination of EPI-7386 and Enzalutamide for prostate cancer because it offers a novel approach to treatment. EPI-7386 is a next-generation androgen receptor inhibitor, which means it targets the cancer cells more precisely and effectively than traditional treatments like Enzalutamide alone. This combination aims to enhance the effectiveness of existing therapies by blocking the pathways that cancer cells use to grow and spread. By potentially improving treatment outcomes and reducing resistance, this innovative duo could represent a significant advancement in prostate cancer care.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

This trial will evaluate the combination of EPI-7386 and Enzalutamide for treating prostate cancer. Studies have shown mixed results regarding the effectiveness of EPI-7386 with Enzalutamide. Specifically, research indicates that when used together, 88% of patients experienced a significant drop in PSA levels, suggesting tumor reduction. However, another study found that this combination was not more effective than using Enzalutamide alone, with Enzalutamide sometimes leading to better results on its own. Despite these mixed findings, researchers continue to investigate the potential benefits of using both drugs together in this trial. ^{1 3 4 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 (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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05075577

Study Details | NCT05075577 | EPI-7386 in Combination ... Study was terminated early due to a lack of improved efficacy. EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC.

2. onclive.com onclive.com/view/essa-discontinues-phase-2-study-of-masofaniten-plus-enzalutamide-in-mcrpc

ESSA Discontinues Phase 2 Study of Masofaniten Plus ... Interim results showed a PSA90 response rate of 64% for the combination therapy versus 73% for enzalutamide monotherapy.

3. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-prostate-cancer/154810-esmo-2024-phase-1-2-trial-of-oral-masofaniten-epi-7386-in-combination-with-enzalutamide-compared-to-enzalutamide-alone-in-metastatic-castration-resistant-prostate-cancer-mcrpc-subjects.html

Phase 1/2 Trial of Oral Masofaniten (EPI-7386 ... - UroToday A total of 88% of the patients dosed with masofaniten + enzalutamide achieved a PSA decline > 90%; With a current median follow up of 15.2 months, time to event ...

4. urologytimes.com urologytimes.com/view/masofaniten-plus-enzalutamide-shows-promise-in-mcrpc

Masofaniten plus enzalutamide shows promise in mCRPC Among patients across all 4 cohorts of the study, 88% (14/16 patients) achieved PSA50, 81% (13/16 patients) achieved PSA90, 69% (11/16 patients) ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT396108

Phase 1/2 study of EPI-7386 in combination with ... PK results demonstrated enz exposure was minimally impacted by EPI-7386, while, as expected, EPI-7386 exposure was reduced 60-80% by enz (well-established ...

6. onclive.com onclive.com/view/masofaniten-plus-enzalutamide-demonstrates-safety-and-durable-responses-in-mcrpc

Masofaniten Plus Enzalutamide Demonstrates Safety and ... Masofaniten administered in combination with enzalutamide (Xtandi) was tolerable, pharmacokinetically active, and led to a decrease in prostate- ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06312670

NCT06312670 | Combining EPI-7386 With Enzalutamide ... The purpose of this study is to study the effects of EPI-7386 in combination with Enzalutamide on participants diagnosed with prostate cancer.