A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer
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
2 other identifiers
interventional
142
1 country
36
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2015
Longer than P75 for phase_2
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 30, 2015
CompletedFirst Posted
Study publicly available on registry
April 2, 2015
CompletedStudy Start
First participant enrolled
April 29, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 26, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
April 16, 2020
CompletedResults Posted
Study results publicly available
May 11, 2021
CompletedMay 11, 2021
June 1, 2020
3.4 years
March 30, 2015
April 17, 2021
April 17, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Part B: Progression Free Survival (PFS)
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 Outcomes (4)
Part B: Time to Disease Progression (TTP)
Randomization to Objective Disease Progression (Up To 34 Months)
Part B: Percentage of Participants With Prostate Specific Antigen Response
12 Weeks
Part A: Pharmacokinetic (PK): Area Under the Concentration-time Curve Over the Dosing Interval (AUCτ) of LY3023414
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])
Randomization to Second Measured Complete Response or Partial Response (Up To 34 Months)
Study Arms (3)
Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD
EXPERIMENTALParticipants 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.
Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD
EXPERIMENTALParticipants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).
Part B: Placebo + 160 mg Enzalutamide QD
ACTIVE COMPARATORParticipants received placebo in combination with 160 mg enzalutamide QD.
Interventions
Administered orally
Administered orally
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eli Lilly and Companylead
- Sarah Cannoncollaborator
Study Sites (36)
Urology Centers of Alabama, P.C.
Homewood, Alabama, 35209, United States
Highlands Oncology Group
Fayetteville, Arkansas, 72703, United States
Prostate Oncology Specialists
Marina del Rey, California, 90292, United States
Sharp Memorial Hospital
San Diego, California, 92123, United States
Florida Cancer Specialists
Fort Myers, Florida, 33901, United States
Florida Cancer Specialists North
St. Petersburg, Florida, 33705, United States
Florida Cancer Specialists East
West Palm Beach, Florida, 33401, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Fort Wayne Oncology & Hematology
Fort Wayne, Indiana, 46845, United States
Indiana Cancer Pavilion
Indianapolis, Indiana, 46202-5286, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Minnesota Oncology/Hematology PA
Minneapolis, Minnesota, 55404, United States
Urology Cancer Center
Omaha, Nebraska, 68130, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89148, United States
Garden State Urology
Morristown, New Jersey, 07960, United States
Delaware Valley Urology
Voorhees Township, New Jersey, 08043, United States
Associated Medical Professionals of NY
Syracuse, New York, 13210, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, 45242, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Oregon Urology Institute
Springfield, Oregon, 97477, United States
Northwest Cancer Specialists PC
Tualatin, Oregon, 97062, United States
Urological Associates of Lancaster
Lancaster, Pennsylvania, 17604, United States
Univ of Pittsburgh Cancer Inst. (UPCI)
Pittsburgh, Pennsylvania, 15213, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572, United States
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, 37203, United States
Tennessee Oncology PLLC
Nashville, Tennessee, 37203, United States
Urology Associates
Nashville, Tennessee, 37209, United States
Southwestern Medical Center - Dallas
Dallas, Texas, 75390, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Fort Worth, Texas, 76104, United States
Texas Oncology-Memorial City
Houston, Texas, 77024, United States
US Oncology
The Woodlands, Texas, 77380, United States
University of Virginia Health System
Charlottesville, Virginia, 22903, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Virginia Oncology Associates
Norfolk, Virginia, 23502, United States
Swedish Medical Center
Seattle, Washington, 98104, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
Sweeney CJ, Percent IJ, Babu S, Cultrera JL, Mehlhaff BA, Goodman OB, Morris DS, Schnadig ID, Albany C, Shore ND, Sieber PR, Guba SC, Zhang W, Wacheck V, Donoho GP, Szpurka AM, Callies S, Lin BK, Bendell JC. Phase Ib/II Study of Enzalutamide with Samotolisib (LY3023414) or Placebo in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2022 Jun 1;28(11):2237-2247. doi: 10.1158/1078-0432.CCR-21-2326.
PMID: 35363301DERIVED
Related Links
MeSH Terms
Interventions
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 30, 2015
First Posted
April 2, 2015
Study Start
April 29, 2015
Primary Completion
September 26, 2018
Study Completion
April 16, 2020
Last Updated
May 11, 2021
Results First Posted
May 11, 2021
Record last verified: 2020-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
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.