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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 : December 15, 2022
Sponsor:
Information provided by (Responsible Party):
ESSA Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE September 14, 2021
First Posted Date  ICMJE October 13, 2021
Last Update Posted Date December 15, 2022
Actual Study Start Date  ICMJE December 21, 2021
Estimated Primary Completion Date August 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2021)
  • 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 >50% (PSA50) at Week 12 [ Time Frame: Baseline to Week 12 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC
Official Title  ICMJE A Phase 1/2 Study of EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With Metastatic Castration-Resistant Prostate Cancer
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Enzalutamide
    Daily oral dose of enzalutamide
  • Drug: EPI-7386 with Enzalutamide
    Daily oral dose of EPI-7386 in combination of enzalutamide
Study Arms  ICMJE
  • Experimental: Phase 1 Cohort 1
    600 mg EPI-7386 in combination of Enzalutamide120 mg
    Intervention: Drug: EPI-7386 with Enzalutamide
  • Experimental: Phase 1 Cohort 2
    800 mg EPI-7386 in combination of Enzalutamide120 mg
    Intervention: Drug: EPI-7386 with Enzalutamide
  • Experimental: Phase 1 Cohort 3
    1000 mg EPI-7386 in combination of Enzalutamide120 mg
    Intervention: Drug: EPI-7386 with Enzalutamide
  • Experimental: Phase 1 Cohort 4
    RP2D mg EPI-7386 in combination of Enzalutamide160 mg
    Intervention: Drug: EPI-7386 with Enzalutamide
  • Experimental: Phase 1 Dose Expansion
    RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg
    Intervention: Drug: EPI-7386 with Enzalutamide
  • Experimental: Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1)
    RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg
    Intervention: Drug: EPI-7386 with Enzalutamide
  • Active Comparator: Phase 2 Enzalutamide single agent
    Enzalutamide 160 mg
    Intervention: Drug: Enzalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 7, 2021)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2026
Estimated Primary Completion Date August 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Karen Villaluna 650-449-8400 kvillaluna@essapharma.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05075577
Other Study ID Numbers  ICMJE EPI-7386-CS-010
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party ESSA Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE ESSA Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account ESSA Pharmaceuticals
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP