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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05075577




Registration number
NCT05075577
Ethics application status
Date submitted
14/09/2021
Date registered
13/10/2021
Date last updated
13/05/2024

Titles & IDs
Public title
EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC
Scientific 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
Secondary ID [1] 0 0
EPI-7386-CS-010
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Enzalutamide
Treatment: Drugs - EPI-7386 with Enzalutamide

Experimental: Phase 1 Cohort 1 - 600 mg QD EPI-7386 in combination of Enzalutamide120 mg

Experimental: Phase 1 Cohort 2 - 800 mg QD EPI-7386 in combination of Enzalutamide120 mg

Experimental: Phase 1 Cohort 3 - 600 mg BID EPI-7386 in combination of Enzalutamide120 mg

Experimental: Phase 1 Cohort 4 - RP2D mg EPI-7386 in combination of Enzalutamide160 mg

Experimental: Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1) - RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg

Active Comparator: Phase 2 Enzalutamide single agent - Enzalutamide 160 mg


Treatment: Drugs: Enzalutamide
Daily oral dose of enzalutamide

Treatment: Drugs: EPI-7386 with Enzalutamide
Daily oral dose of EPI-7386 in combination of enzalutamide
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Incidence of Dose Limiting Toxicities
Timepoint [1] 0 0
Baseline to End of Cycle 1 (each cycle is 28 days)
Primary outcome [2] 0 0
Phase 1: Incidence of treatment emergent adverse events
Timepoint [2] 0 0
Baseline to 30 days after last dose of study drug
Primary outcome [3] 0 0
Phase 1: Incidence of laboratory abnormalities as a measure of safety and tolerability of EPI-7386
Timepoint [3] 0 0
Baseline to 30 days after last dose of study drug
Primary outcome [4] 0 0
Phase 1: Changes in ECOG performance status
Timepoint [4] 0 0
Baseline to 30 days after last dose of study drug
Primary outcome [5] 0 0
Phase 2: Proportion of subjects with a prostate-specific antigen decline of >50% (PSA50) at Week 12
Timepoint [5] 0 0
Baseline to Week 12

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2026
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,VIC
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [4] 0 0
Eastern Health - Box Hill
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
South Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ESSA Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05075577
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Karen Villaluna
Address 0 0
Country 0 0
Phone 0 0
650-449-8400
Fax 0 0
Email 0 0
kvillaluna@essapharma.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05075577