Clinical trial NCT02407054: A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer Metastatic
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Sarah Cannon
First posted: 2015-04-02
Enrollment: 142
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part B: Progression Free Survival (PFS)
timeFrame: Randomization to Measured Progressive Disease or Death from Any Cause (Up To 34 Months)
Secondary outcomes:
measure: Part B: Time to Disease Progression (TTP)
timeFrame: Randomization to Objective Disease Progression (Up To 34 Months)
measure: Part B: Percentage of Participants With Prostate Specific Antigen Response
timeFrame: 12 Weeks
measure: Part A: Pharmacokinetic (PK): Area Under the Concentration-time Curve Over the Dosing Interval (AUCτ) of LY3023414
timeFrame: 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
measure: Part B: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
timeFrame: Randomization to Second Measured Complete Response or Partial Response (Up To 34 Months)
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Urology Centers of Alabama, P.C.
state: Alabama
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Marina Del Rey
country: United States
facility: Prostate Oncology Specialists
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists North
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists East
state: Florida
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Cancer Pavilion
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: Minnesota Oncology/Hematology PA
state: Minnesota
city: Omaha
country: United States
facility: Urology Cancer Center
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Morristown
country: United States
facility: Garden State Urology
state: New Jersey
city: Voorhees
country: United States
facility: Delaware Valley Urology
state: New Jersey
city: Syracuse
country: United States
facility: Associated Medical Professionals of NY
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Springfield
country: United States
facility: Oregon Urology Institute
state: Oregon
city: Tualatin
country: United States
facility: Northwest Cancer Specialists PC
state: Oregon
city: Lancaster
country: United States
facility: Urological Associates of Lancaster
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh Cancer Inst. (UPCI)
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute SCRI
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: Dallas
country: United States
facility: Southwestern Medical Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Texas Oncology-Memorial City
state: Texas
city: The Woodlands
country: United States
facility: US Oncology
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.