A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer
- Conditions
- Prostate Cancer Metastatic
- Interventions
- Registration Number
- NCT02407054
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 142
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD LY3023414 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. Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD LY3023414 Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD). Part B: Placebo + 160 mg Enzalutamide QD Placebo Participants received placebo in combination with 160 mg enzalutamide QD. Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD Enzalutamide 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. Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD Enzalutamide Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD). Part B: Placebo + 160 mg Enzalutamide QD Enzalutamide Participants received placebo in combination with 160 mg enzalutamide QD.
- Primary Outcome Measures
Name Time Method Part B: Progression Free Survival (PFS) 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).
- Secondary Outcome Measures
Name Time Method Part B: Time to Disease Progression (TTP) 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).
Part B: Percentage of Participants With Prostate Specific Antigen Response 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.
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 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 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) 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.
Trial Locations
- Locations (36)
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Fort Wayne Oncology & Hematology
🇺🇸Fort Wayne, Indiana, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists East
🇺🇸West Palm Beach, Florida, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Associated Medical Professionals of NY
🇺🇸Syracuse, New York, United States
Oncology Hematology Care Inc
🇺🇸Cincinnati, Ohio, United States
Univ of Pittsburgh Cancer Inst. (UPCI)
🇺🇸Pittsburgh, Pennsylvania, United States
Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Texas Oncology-Memorial City
🇺🇸Houston, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Urology Centers of Alabama, P.C.
🇺🇸Homewood, Alabama, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Indiana Cancer Pavilion
🇺🇸Indianapolis, Indiana, United States
Florida Cancer Specialists North
🇺🇸Saint Petersburg, Florida, United States
Delaware Valley Urology
🇺🇸Voorhees, New Jersey, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
US Oncology
🇺🇸The Woodlands, Texas, United States
Minnesota Oncology/Hematology PA
🇺🇸Minneapolis, Minnesota, United States
Sarah Cannon Research Institute SCRI
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology PLLC
🇺🇸Nashville, Tennessee, United States
Urology Associates
🇺🇸Nashville, Tennessee, United States
Urology Cancer Center
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Prostate Oncology Specialists
🇺🇸Marina Del Rey, California, United States
Urological Associates of Lancaster
🇺🇸Lancaster, Pennsylvania, United States
Garden State Urology
🇺🇸Morristown, New Jersey, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Oregon Urology Institute
🇺🇸Springfield, Oregon, United States
Northwest Cancer Specialists PC
🇺🇸Tualatin, Oregon, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Fort Worth, Texas, United States