Clinical trial NCT05075577: EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Lead sponsor: ESSA Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-10-13
Enrollment: 77
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.
* Not a candidate for enzalutamide treatment.
* Patients with rare hereditary problems of fructose intolerance.

Primary outcomes:
measure: Phase 1: Incidence of Dose Limiting Toxicities
timeFrame: Baseline to End of Cycle 1 (each cycle is 28 days)
measure: Phase 1: Incidence of treatment emergent adverse events
timeFrame: Baseline to 30 days after last dose of study drug
measure: Phase 1: Incidence of laboratory abnormalities as a measure of safety and tolerability of EPI-7386
timeFrame: Baseline to 30 days after last dose of study drug
measure: Phase 1: Changes in ECOG performance status
timeFrame: Baseline to 30 days after last dose of study drug
measure: Phase 2: Proportion of subjects with a prostate-specific antigen decline of >90% (PSA90) at Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Urology
state: Arizona
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Chesapeake Urology Associates
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Saint Louis
country: United States
facility: Washington University Siteman Cancer Center
state: Missouri
city: Omaha
country: United States
facility: Urology Cancer Center
state: Nebraska
city: Buffalo
country: United States
facility: Great Lakes Cancer Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: OHSU Knight Cancer Instititue
state: Oregon
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Garran
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital Sydney
state: New South Wales
city: Box Hill
country: Australia
facility: Eastern Health
state: Victoria
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Calgary
country: Canada
facility: Prostate Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre, Hamilton, ON L8V 5C2
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
References: