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

Prostate Cancer Clinical Trial

Official title:

Overcoming Drug Resistance in Metastatic Castration-resistant Prostate Cancer With Novel Combination of TGF-β Receptor Inhibitor LY2157299 and Enzalutamide: a Randomized Multi-site Phase II Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02452008
• Other study ID #: J1557
• Secondary ID: IRB00065746
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 3, 2016
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide
160mg of enzalutamide is administered orally once a day on days 1-28 of each cycle.
• LY2157299
150 mg of LY2157299 is administered orally twice a day on days 1-14 of each cycle.

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Number of patients experiencing treatment-related toxicities		4 years