Prostate CancerPhase 1/2NCT05075577
EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC
A Phase 1/2 study testing Enzalutamide and EPI-7386 with Enzalutamide in people with Prostate Cancer, run by ESSA Pharmaceuticals at 24 sites in 3 countries.
Trial summary
This is a Phase 1/2 study of EPI-7386 orally administered in combination with enzalutamide in subjects with mCRPC. Phase 1 of the study will be a single-arm dose escalation study of EPI-7386 in combination with a fixed dose of enzalutamide. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Enzalutamide and EPI-7386 with Enzalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 24 sitesin 3 countries
- Study dates
- 21 Dec 2021to 14 Jan 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males ≥18 years.
- Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
- Evidence of castration-resistant prostate cancer (CRPC).
- Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
- Naïve to second generation anti-androgens.
- Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy or history of bilateral orchiectomy, with castrate level testosterone.
- Serum testosterone ≤1.73 nmol/L (50 ng/dL).
- Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days prior to the start of study treatment.
- Demonstrate adequate organ function.
Who cannot join
- Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
- Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days prior to the start of study treatment.
- Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 28 days prior to the start of study treatment or plans to initiate during the study.
- Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs within 28 days of the first dose of study treatment.
- Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study treatment.
- Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study treatment.
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- Received a blood transfusion within 28 days of hematologic screening labs.
- Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 28 days before signing of informed consent.
- Spinal cord compression.
- Diagnosis of another clinically significant malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or non-invasive malignancies.
- Gastrointestinal issues affecting absorption.
- Significant cardiovascular disease.
- Known history of seizure or conditions that may pre-dispose them to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation.
- Concurrent disease or any clinically significant abnormality.
- Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
- Use of strong inhibitors of CYP2C8.
- Use of strong inducers of CYP3A.
- Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and CYP2B6.
- Use of granulocyte colony stimulating factor within 7 days prior to screening laboratories.
- Not a candidate for enzalutamide treatment.
- Patients with rare hereditary problems of fructose intolerance.
Trial locations and contacts
24 sites in 3 countries.
24 sites in 3 countries
United States13 sites
Chesapeake Urology Associates
Baltimore, Maryland, 21204
Johns Hopkins University
Baltimore, Maryland, 21231
Great Lakes Cancer Center
Buffalo, New York, 14203
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14203
University of Wisconsin
Madison, Wisconsin, 53792
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Urology Cancer Center
Omaha, Nebraska, 68130
Hematology Oncology Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952
OHSU Knight Cancer Instititue
Portland, Oregon, 97239
Washington University Siteman Cancer Center
St Louis, Missouri, 63110
Moffitt Cancer Center
Tampa, Florida, 33612
Arizona Urology
Tucson, Arizona, 85741
Canada7 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Prostate Cancer Centre
Calgary, Alberta, T2V 1P9
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Juravinski Cancer Centre, Hamilton, ON L8V 5C2
Hamilton, Ontario, L8V 5C2
Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, H2X 0A9
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9
Australia4 sites
Eastern Health
Box Hill, Victoria, 3128
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
St. Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
The Canberra Hospital
Garran, Australian Capital Territory, 2605
About this study
Official title: A Phase 1/2 Study of EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with Metastatic Castration-Resistant Prostate Cancer
This is a Phase 1/2 study of EPI-7386 orally administered in combination with enzalutamide in subjects with mCRPC.
Phase 1 of the study will be a single-arm dose escalation study of EPI-7386 in combination with a fixed dose of enzalutamide. This portion of the study will primarily evaluate the safety and tolerability of the drug combination and establish the RP2CDs for EPI-7386 and enzalutamide when dosed in combination. In addition, blood sampling will be conducted for PK evaluation to assess the potential DDI between the two drugs.
Read more
Once the RP2CD for each drug has been established, Phase 2 of the study will commence. Phase 2 is a two-arm, randomized (2:1), open-label study. Approximately 120 subjects will be randomized 2:1 to:
- Group 1: EPI-7386 at the RP2CD + enzalutamide(depending on the results of the Phase 1) (n=80)
- Group 2: Enzalutamide single agent (n=40) The planned dose of enzalutamide and EPI-7386 for the combination arm will be those determined in the Phase 1 of this study based on safety and exposure data. Subjects may remain on study treatment as long as they are tolerating treatment without disease progression based on RECIST v1.1 and/or PCWG3.
- Conditions
- Prostate Cancer
- Being tested
- Enzalutamide, EPI-7386 with Enzalutamide
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnzalutamideDrug
Daily oral dose of enzalutamide
EPI-7386 with EnzalutamideDrug
Daily oral dose of EPI-7386 in combination of enzalutamide
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Cohort 1 | Experimental | 600 mg QD EPI-7386 in combination of Enzalutamide120 mg Receives: Drug: EPI-7386 with Enzalutamide |
| Phase 1 Cohort 2 | Experimental | 800 mg QD EPI-7386 in combination of Enzalutamide120 mg Receives: Drug: EPI-7386 with Enzalutamide |
| Phase 1 Cohort 3 | Experimental | 600 mg BID EPI-7386 in combination of Enzalutamide120 mg Receives: Drug: EPI-7386 with Enzalutamide |
| Phase 1 Cohort 4 | Experimental | RP2D mg EPI-7386 in combination of Enzalutamide160 mg Receives: Drug: EPI-7386 with Enzalutamide |
| Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1) | Experimental | RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg Receives: Drug: EPI-7386 with Enzalutamide |
| Phase 2 Enzalutamide single agent | Active comparator | Enzalutamide 160 mg Receives: Drug: Enzalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Incidence of Dose Limiting Toxicities
Characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for AEs [NCI CTCAE version 5.0]), timing in relation to study treatment administration, seriousness, and relationship to study treatment.
Measured: Baseline to End of Cycle 1 (each cycle is 28 days)
Phase 1: Incidence of treatment emergent adverse events
Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.
Measured: Baseline to 30 days after last dose of study drug
Phase 1: Incidence of laboratory abnormalities as a measure of safety and tolerability of EPI-7386
Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.
Measured: Baseline to 30 days after last dose of study drug
Phase 1: Changes in ECOG performance status
Measured: Baseline to 30 days after last dose of study drug
Phase 2: Proportion of subjects with a prostate-specific antigen decline of >90% (PSA90) at Week 12
Measured: Baseline to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2021
- Study start21 Dec 2021
- Primary completion31 Oct 2024
- Study completion14 Jan 2025
Why it stopped: Study was terminated early due to a lack of improved efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- ESSA Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05075577
- Sponsor's protocol ID
- EPI-7386-CS-010
- Status last verified
- Feb 2025
- First submitted
- 14 Sep 2021
- Last updated
- 28 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with Metastatic Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT05075577
- Acronym / sponsor ID
- EPI-7386-CS-010
- Conditions
- Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated early due to a lack of improved efficacy.
- Enrolment
- 77 participants (actual)
- Lead sponsor
- ESSA PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 Dec 2021 (actual)
- Primary completion
- 31 Oct 2024 (actual)
- Study completion
- 14 Jan 2025 (actual)
- First posted
- 13 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1/2 study of EPI-7386 orally administered in combination with enzalutamide in subjects with mCRPC.
Phase 1 of the study will be a single-arm dose escalation study of EPI-7386 in combination with a fixed dose of enzalutamide. This portion of the study will primarily evaluate the safety and tolerability of the drug combination and establish the RP2CDs for EPI-7386 and enzalutamide when dosed in combination. In addition, blood sampling will be conducted for PK evaluation to assess the potential DDI between the two drugs.
Once the RP2CD for each drug has been established, Phase 2 of the study will commence. Phase 2 is a two-arm, randomized (2:1), open-label study. Approximately 120 subjects will be randomized 2:1 to:
- Group 1: EPI-7386 at the RP2CD + enzalutamide(depending on the results of the Phase 1) (n=80)
- Group 2: Enzalutamide single agent (n=40) The planned dose of enzalutamide and EPI-7386 for the combination arm will be those determined in the Phase 1 of this study based on safety and exposure data. Subjects may remain on study treatment as long as they are tolerating treatment without disease progression based on RECIST v1.1 and/or PCWG3.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Cohort 1 | Experimental | Drug: EPI-7386 with Enzalutamide600 mg QD EPI-7386 in combination of Enzalutamide120 mg |
| Phase 1 Cohort 2 | Experimental | Drug: EPI-7386 with Enzalutamide800 mg QD EPI-7386 in combination of Enzalutamide120 mg |
| Phase 1 Cohort 3 | Experimental | Drug: EPI-7386 with Enzalutamide600 mg BID EPI-7386 in combination of Enzalutamide120 mg |
| Phase 1 Cohort 4 | Experimental | Drug: EPI-7386 with EnzalutamideRP2D mg EPI-7386 in combination of Enzalutamide160 mg |
| Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1) | Experimental | Drug: EPI-7386 with EnzalutamideRP2D mg EPI-7386 in combination of Enzalutamide RP2D mg |
| Phase 2 Enzalutamide single agent | Active comparator | Drug: EnzalutamideEnzalutamide 160 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Males ≥18 years.
- Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
- Evidence of castration-resistant prostate cancer (CRPC).
- Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
- Naïve to second generation anti-androgens.
Key exclusion criteria (21 listed)
- Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
- Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days prior to the start of study treatment.
- Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 28 days prior to the start of study treatment or plans to initiate during the study.
- Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs within 28 days of the first dose of study treatment.
- Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnzalutamideDaily oral dose of enzalutamide | Drug | Phase 2 Enzalutamide single agent |
| EPI-7386 with EnzalutamideDaily oral dose of EPI-7386 in combination of enzalutamide | Drug | Phase 1 Cohort 1, Phase 1 Cohort 2, Phase 1 Cohort 3, Phase 1 Cohort 4, Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1) |
Primary outcome
Phase 1: Incidence of Dose Limiting Toxicities
Time frame: Baseline to End of Cycle 1 (each cycle is 28 days)
Characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for AEs [NCI CTCAE version 5.0]), timing in relation to study treatment administration, seriousness, and relationship to study treatment.
Phase 1: Incidence of treatment emergent adverse events
Time frame: Baseline to 30 days after last dose of study drug
Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.
Phase 1: Incidence of laboratory abnormalities as a measure of safety and tolerability of EPI-7386
Time frame: Baseline to 30 days after last dose of study drug
Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.
Phase 1: Changes in ECOG performance status
Time frame: Baseline to 30 days after last dose of study drug
Phase 2: Proportion of subjects with a prostate-specific antigen decline of >90% (PSA90) at Week 12
Time frame: Baseline to Week 12
Results and safety
The study was stopped early (reason given: Study was terminated early due to a lack of improved efficacy.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Enzalutamide and EPI-7386 with Enzalutamide in people with Prostate Cancer, run by ESSA Pharmaceuticals at 24 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study was terminated early due to a lack of improved efficacy.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Incidence of Dose Limiting Toxicities (time frame: Baseline to End of Cycle 1 (each cycle is 28 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.