A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer

NCT ID: NCT02407054

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-29
• Study Completion Date: 2020-04-16

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.

Conditions

Prostate Cancer Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

LY3023414

Intervention Type: DRUG

Administered orally

Enzalutamide

Intervention Type: DRUG

Administered orally

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).

Group Type: EXPERIMENTAL

LY3023414

Intervention Type: DRUG

Administered orally

Enzalutamide

Intervention Type: DRUG

Administered orally

Part B: Placebo + 160 mg Enzalutamide QD

Participants received placebo in combination with 160 mg enzalutamide QD.

Group Type: ACTIVE_COMPARATOR

Enzalutamide

Intervention Type: DRUG

Administered orally

Placebo

Intervention Type: DRUG

Administered orally

Interventions

LY3023414

Administered orally

Intervention Type: DRUG

Enzalutamide

Administered orally

Intervention Type: DRUG

Placebo

Administered orally

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sarah Cannon

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Eli Lilly and Company

Locations

Urology Centers of Alabama, P.C.

Homewood, Alabama, United States

Highlands Oncology Group

Fayetteville, Arkansas, United States

Prostate Oncology Specialists

Marina del Rey, California, United States

Sharp Memorial Hospital

San Diego, California, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Florida Cancer Specialists North

St. Petersburg, Florida, United States

Florida Cancer Specialists East

West Palm Beach, Florida, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Fort Wayne Oncology & Hematology

Fort Wayne, Indiana, United States

Indiana Cancer Pavilion

Indianapolis, Indiana, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Minnesota Oncology/Hematology PA

Minneapolis, Minnesota, United States

Urology Cancer Center

Omaha, Nebraska, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Garden State Urology

Morristown, New Jersey, United States

Delaware Valley Urology

Voorhees Township, New Jersey, United States

Associated Medical Professionals of NY

Syracuse, New York, United States

Oncology Hematology Care Inc

Cincinnati, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Oregon Urology Institute

Springfield, Oregon, United States

Northwest Cancer Specialists PC

Tualatin, Oregon, United States

Urological Associates of Lancaster

Lancaster, Pennsylvania, United States

Univ of Pittsburgh Cancer Inst. (UPCI)

Pittsburgh, Pennsylvania, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, United States

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Urology Associates

Nashville, Tennessee, United States

Southwestern Medical Center - Dallas

Dallas, Texas, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Fort Worth, Texas, United States

Texas Oncology-Memorial City

Houston, Texas, United States

US Oncology

The Woodlands, Texas, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Swedish Medical Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35363301 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.lillytrialguide.com/EN-us/studies/cancer/cbbd

Click here for more information about this study: A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer

Other Identifiers

I6A-MC-CBBD

Identifier Type: OTHER

Identifier Source: secondary_id

15798

Identifier Type: -

Identifier Source: org_study_id