Study of TGF-β Receptor Inhibitor Galunisertib (LY2157299) and Enzalutamide in Metastatic Castration-resistant Prostate Cancer

NCT02452008 | Active Not Recruiting Phase 2

• 2 other identifiers: J1557IRB00065746
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this study is to compare the progression free survival (PFS) of patients with metastatic castration-resistant prostate cancer treated with enzalutamide in combination with LY2157299 (Arm 1) versus enzalutamide alone (Arm 2).

Conditions

Prostate Cancer

Keywords

metastatic castration-resistant prostate cancer; enzalutamide; LY2157299; TGF-β receptor inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression free survival in patients with metastatic castration-resistant prostate cancer treated with enzalutamide and LY2157299 (Arm 1) versus enzalutamide alone (Arm 2) using RECIST 1.1 criteria.

  4 years

Secondary Outcomes (3)

• Tumor marker kinetics (PSA) in patients with metastatic castration-resistant prostate cancer treated with enzalutamide and LY2157299 (Arm 1) versus enzalutamide alone (Arm 2).

  4 years

• Overall survival (OS) in patients with metastatic castration-resistant prostate cancer treated with enzalutamide and LY2157299 (Arm 1) versus enzalutamide alone (Arm 2).

  4 years

• Number of patients experiencing treatment-related toxicities

  4 years

Study Arms (2)

Arm 1: Enzalutamide with LY2157299

EXPERIMENTAL

Drug: Enzalutamide; Drug: LY2157299

Arm 2: Enzalutamide alone

EXPERIMENTAL

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

160mg of enzalutamide is administered orally once a day on days 1-28 of each cycle.

Also known as: XTANDI

Arm 1: Enzalutamide with LY2157299; Arm 2: Enzalutamide alone

LY2157299 DRUG

150 mg of LY2157299 is administered orally twice a day on days 1-14 of each cycle.

Also known as: TGF-β receptor inhibitor

Arm 1: Enzalutamide with LY2157299

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have metastatic castration-resistant prostate cancer
• Must have had prior abiraterone treatment
• Life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 2
• Age ≥18 years
• Have measurable disease
• Patients acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).
• Ability to take oral medication
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests
• Must use acceptable form of birth control while on study
• Ability to understand and willingness to sign a written informed consent document

You may not qualify if:

• Known history or evidence of brain metastases
• Prior chemotherapy for metastatic disease in castration-resistant prostate cancer
• Had surgery within 4 weeks prior to the first dose of study drug
• Had radiation, biological, or other investigational cancer therapy within 2 weeks prior to the first dose of study drug
• Had second-line hormonal therapy within 2 weeks prior to the first dose of study drug
• Systemic steroids within 1 weeks prior to the first dose of study drug
• Had prior enzalutamide, ARN-509, or galeterone therapy
• Have moderate or severe cardiovascular disease
• Have a history of a seizure
• Have uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements
• Have a history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythmatosus (SLE) autoimmune vasculitis (e.g., Wegener's Granulomatosis), central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin (e.g., Guillian-Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis)
• Have known history of infection with HIV, hepatitis B, or hepatitis C

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Eli Lilly and Company: collaborator
• National Capital Foundation: collaborator

Study Sites (4)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• Rodriguez Y, Unno K, Truica MI, Chalmers ZR, Yoo YA, Vatapalli R, Sagar V, Yu J, Lysy B, Hussain M, Han H, Abdulkadir SA. A Genome-Wide CRISPR Activation Screen Identifies PRRX2 as a Regulator of Enzalutamide Resistance in Prostate Cancer. Cancer Res. 2022 Jun 6;82(11):2110-2123. doi: 10.1158/0008-5472.CAN-21-3565.

  PMID: 35405009 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; LY-2157299

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Channing Paller, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 22, 2015
• Study Start: May 3, 2016
• Primary Completion: December 8, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

US (4)