Clinical trial NCT02452008: Study of TGF-β Receptor Inhibitor Galunisertib (LY2157299) and Enzalutamide in Metastatic Castration-resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: metastatic castration-resistant prostate cancer
enzalutamide
LY2157299
TGF-β receptor inhibitor
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
name: National Capital Foundation
First posted: 2015-05-22
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 4 years
Secondary outcomes:
measure: Tumor marker kinetics (PSA) in patients with metastatic castration-resistant prostate cancer treated with enzalutamide and LY2157299 (Arm 1) versus enzalutamide alone (Arm 2).
timeFrame: 4 years
measure: Overall survival (OS) in patients with metastatic castration-resistant prostate cancer treated with enzalutamide and LY2157299 (Arm 1) versus enzalutamide alone (Arm 2).
timeFrame: 4 years
measure: Number of patients experiencing treatment-related toxicities
timeFrame: 4 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Channing Paller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.