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EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC

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ClinicalTrials.gov Identifier: NCT05075577
Recruitment Status : Recruiting
First Posted : October 13, 2021
Last Update Posted : July 5, 2022
Sponsor:
Information provided by (Responsible Party):
ESSA Pharmaceuticals

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Enzalutamide Drug: EPI-7386 with Enzalutamide Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 21, 2021
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : January 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 Cohort 1
600 mg EPI-7386 in combination of Enzalutamide120 mg
Drug: EPI-7386 with Enzalutamide
Daily oral dose of EPI-7386 in combination of enzalutamide

Experimental: Phase 1 Cohort 2
800 mg EPI-7386 in combination of Enzalutamide120 mg
Drug: EPI-7386 with Enzalutamide
Daily oral dose of EPI-7386 in combination of enzalutamide

Experimental: Phase 1 Cohort 3
1000 mg EPI-7386 in combination of Enzalutamide120 mg
Drug: EPI-7386 with Enzalutamide
Daily oral dose of EPI-7386 in combination of enzalutamide

Experimental: Phase 1 Cohort 4
RP2D mg EPI-7386 in combination of Enzalutamide160 mg
Drug: EPI-7386 with Enzalutamide
Daily oral dose of EPI-7386 in combination of enzalutamide

Experimental: Phase 1 Dose Expansion
RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg
Drug: EPI-7386 with Enzalutamide
Daily oral dose of EPI-7386 in combination of enzalutamide

Experimental: Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1)
RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg
Drug: EPI-7386 with Enzalutamide
Daily oral dose of EPI-7386 in combination of enzalutamide

Active Comparator: Phase 2 Enzalutamide single agent
Enzalutamide 160 mg
Drug: Enzalutamide
Daily oral dose of enzalutamide




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Phase 1: Changes in ECOG performance status [ Time Frame: Baseline to 30 days after last dose of study drug ]
  5. Phase 2: Proportion of subjects with a prostate-specific antigen decline of >50% (PSA50) at Week 12 [ Time Frame: Baseline to Week 12 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05075577


Contacts
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Contact: Karen Villaluna 650-449-8400 kvillaluna@essapharma.com

Locations
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United States, Florida
Hematology Oncology Associates of the Treasure Coast Recruiting
Port Saint Lucie, Florida, United States, 34952
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21231
United States, New York
Great Lakes Cancer Center Recruiting
Buffalo, New York, United States, 14203
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14203
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53792
Canada, Ontario
Juravinski Cancer Centre, Hamilton, ON L8V 5C2 Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Sponsors and Collaborators
ESSA Pharmaceuticals
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Responsible Party: ESSA Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05075577    
Other Study ID Numbers: EPI-7386-CS-010
First Posted: October 13, 2021    Key Record Dates
Last Update Posted: July 5, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases