A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer

April 17, 2021 updated by: Eli Lilly and Company

A Double-Blinded, Placebo-Controlled, Randomized Phase II Study of Enzalutamide With or Without the PI3 Kinase/mTOR Inhibitor LY3023414 in Men With Metastatic Castration Resistant Prostate Cancer

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY3023414 in combination with enzalutamide in men with prostate cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
142

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Homewood, Alabama, United States, 35209
        • Urology Centers of Alabama, P.C.
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group
    • California
      • Marina Del Rey, California, United States, 90292
        • Prostate Oncology Specialists
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists North
      • West Palm Beach, Florida, United States, 33401
        • Florida Cancer Specialists East
    • Illinois
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Fort Wayne Oncology & Hematology
      • Indianapolis, Indiana, United States, 46202-5286
        • Indiana Cancer Pavilion
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Minnesota Oncology/Hematology PA
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Urology Cancer Center
    • Nevada
      • Las Vegas, Nevada, United States, 89148
        • Comprehensive Cancer Centers of Nevada
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Garden State Urology
      • Voorhees, New Jersey, United States, 08043
        • Delaware Valley Urology
    • New York
      • Syracuse, New York, United States, 13210
        • Associated Medical Professionals of NY
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care Inc
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • Oregon
      • Springfield, Oregon, United States, 97477
        • Oregon Urology Institute
      • Tualatin, Oregon, United States, 97062
        • Northwest Cancer Specialists PC
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17604
        • Urological Associates of Lancaster
      • Pittsburgh, Pennsylvania, United States, 15213
        • Univ of Pittsburgh Cancer Inst. (UPCI)
    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Carolina Urologic Research Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology PLLC
      • Nashville, Tennessee, United States, 37209
        • Urology Associates
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute SCRI
    • Texas
      • Dallas, Texas, United States, 75390
        • Southwestern Medical Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center
      • Houston, Texas, United States, 77024
        • Texas Oncology-Memorial City
      • The Woodlands, Texas, United States, 77380
        • US Oncology
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Health System
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate.
  • Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan.
  • Prostate cancer progression documented by PSA and/or radiographic progression according to prostate cancer working group 2 (PCWG2).
  • Prior abiraterone treatment completed at least 4 weeks prior to cycle 1 day 1. Participants must have failed prior abiraterone treatment.
  • Surgically or medically castrated, with testosterone levels of < 50 nanograms/deciliter.
  • Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
  • Ability to swallow the study drugs whole.
  • Adequate hematologic function.
  • Adequate coagulation parameters, defined as international normalization ratio (INR) ≤ 2.
  • Availability of tumor tissue from any time since diagnosis of prostate cancer disease. If no tumor samples are available the participant might still be eligible following discussion between the investigator and the medical monitor.

Exclusion Criteria:

  • Prior cytotoxic chemotherapy, immunotherapy, a PI3K/AKT/mTOR agent (including TORC1 and TORC2 inhibitors), or RA 223 dichloride for the treatment of castration resistant prostate cancer (CRPC). Participants may have received docetaxel in the hormone-sensitive setting.
  • Prior investigational new generation potent anti-androgen therapy (such as ARN 509).
  • Prior treatment with enzalutamide.
  • Pathological finding consistent with small cell carcinoma of the prostate.
  • Prior systemic treatment with an azole drug (fluconazole, itraconazole) within 4 weeks of cycle 1 day 1.
  • Known brain metastasis.
  • History of (a) seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma); (b) loss of consciousness or transient ischemic attack within 12 months prior to day 1 of cycle 1.
  • Uncontrolled hypertension (systolic blood pressure [BP] ≥ 160 millimeters of mercury [mmHg] or diastolic BP ≥ 95 mmHg).
  • Have serious pre-existing medical conditions (at the discretion of the investigator).
  • Have known acute or chronic leukemia or current hematologic malignancies that, in the judgment of the investigator and sponsor, may affect the interpretation of results.
  • Have insulin-dependent diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c <7%.
  • Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, grade ≥2 diarrhea, and malabsorption syndrome).
  • Have a history of New York Heart Association (NYHA) Class ≥3, QTc interval > 480 milliseconds (ms) on screening electrocardiogram (ECG) per Friderica's formula, unstable angina, or myocardial infarction (MI) in 6 months prior to study drug administration.
  • Clinically significant electrolyte imbalance ≥ grade 2.
  • Currently receiving treatment with therapeutic doses of warfarin sodium.
  • Have initiated treatment with bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents (e.g. denosumab) ≤28 days prior to day 1 of cycle 1.
  • Concurrent serious infections requiring parenteral antibiotic therapy.
  • Have a second primary malignancy that in the judgment of the investigator and medical monitor may affect the interpretation of results.
  • Have an active, known fungal, bacterial, and/or known viral infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD
Participants received 200 milligrams (mg) LY3023414 orally twice daily (BID) during the initial week to assess pharmacokinetics (PK). Thereafter, participants received 200 mg of LY3023414 BID in combination with 160 mg of enzalutamide QD beginning Cycle 1 Day 1. A treatment cycle was defined as 28 days.
Drug: LY3023414
Administered orally
Drug: Enzalutamide
Administered orally
Experimental: Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD
Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).
Drug: LY3023414
Administered orally
Drug: Enzalutamide
Administered orally
Active Comparator: Part B: Placebo + 160 mg Enzalutamide QD
Participants received placebo in combination with 160 mg enzalutamide QD.
Drug: Placebo
Administered orally
Drug: Enzalutamide
Administered orally

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part B: Progression Free Survival (PFS)
Time Frame: Randomization to Measured Progressive Disease or Death from Any Cause (Up To 34 Months)
PFS was defined as the time from randomization until the date of clinical (symptomatic or radiographic) and/or prostate specific antigen (PSA) disease progression per Prostate Cancer Clinical Trials Working Group (PCWG2) or death by any cause regardless of whether the participants withdraws from study drug or receives a subsequent anti-cancer therapy (as determined by the investigator). Participants who have not progressed or died at the time of assessment were censored at the time of the last date of assessment (tumor evaluation or PSA level).
Randomization to Measured Progressive Disease or Death from Any Cause (Up To 34 Months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part B: Time to Disease Progression (TTP)
Time Frame: Randomization to Objective Disease Progression (Up To 34 Months)
TTP was defined as time from randomization until the date of clinical (symptomatic or radiographic) and/or prostate specific antigen (PSA) disease progression per Prostate Cancer Clinical Trials Working Group (PCWG2).
Randomization to Objective Disease Progression (Up To 34 Months)
Part B: Percentage of Participants With Prostate Specific Antigen Response
Time Frame: 12 Weeks
PSA response was defined as more than 50% and 90% reduction from baseline to lowest post baseline value. 95% Confidence Intervals are based on Fisher's Exact Method.
12 Weeks
Part A: Pharmacokinetic (PK): Area Under the Concentration-time Curve Over the Dosing Interval (AUCτ) of LY3023414
Time Frame: Part A: 200 mg LY3023414 + 160 mg Enzalutamide: Cycle 1 Day 15 Pre-dose of LY3023414 and enzalutamide 1.5, 3, and 6 hours post LY3023414 dose

PK: Area under the Concentration-time Curve Over the Dosing Interval (AUCτ) of LY3023414

Time Frame:

Part A LY3023414 200 mg: Day-1 pre-dose, 1.5, 3, and 6 hours post LY3023414 dose, Cycle 1 Day 1 pre-dose of LY3023414 and enzalutamide, and Part A Day 15 Pre-dose of LY3023414 and enzalutamide 1.5, 3, and 6 hours post LY3023414 dose;
Part A: 200 mg LY3023414 + 160 mg Enzalutamide: Cycle 1 Day 15 Pre-dose of LY3023414 and enzalutamide 1.5, 3, and 6 hours post LY3023414 dose
Part B: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Time Frame: Randomization to Second Measured Complete Response or Partial Response (Up To 34 Months)
ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 millimeter (mm), or unequivocal progression of non-target lesions, or 1 or more new lesions.
Randomization to Second Measured Complete Response or Partial Response (Up To 34 Months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sarah Cannon Development Innovations

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 29, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 26, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 16, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 30, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 2, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 15798
  • I6A-MC-CBBD (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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