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

Sponsor
ESSA Pharmaceuticals (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05075577
Collaborator
(none)
150
Enrollment
2
Locations
7
Arms
51
Anticipated Duration (Months)
75
Patients Per Site
1.5
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated 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
Anticipated Study Start Date :
Oct 1, 2021
Anticipated Primary Completion Date :
Aug 1, 2025
Anticipated Study Completion Date :
Jan 1, 2026

Arms and Interventions

ArmIntervention/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

Outcome Measures

Primary Outcome Measures

  1. Phase 1: Incidence of Dose Limiting Toxicities [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 [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 [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 [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 [Baseline to Week 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • 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 compounds known to be strong inducers and strong inhibitors of CYP3A and CYP2C8 within 14 days of the first dose of study drug.

  • 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.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Hematology Oncology Associates of the Treasure CoastPort Saint LucieFloridaUnited States34952
2Great Lakes Cancer CenterBuffaloNew YorkUnited States14203

Sponsors and Collaborators

  • ESSA Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
ESSA Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT05075577
Other Study ID Numbers:
  • EPI-7386-CS-010
First Posted:
Oct 13, 2021
Last Update Posted:
Oct 13, 2021
Last Verified:
Sep 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 13, 2021