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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Enzalutamide
* Drug: LY2157299


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have metastatic castration-resistant prostate cancer Must have had prior abiraterone treatment Life expectancy of greater than 3 months 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), 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Enzalutamide with LY2157299<br> | Drug: Enzalutamide<br>* 160mg of enzalutamide is administered orally once a day on days 1-28 of each cycle.<br>* Other names: XTANDI;Drug: LY2157299<br>* 150 mg of LY2157299 is administered orally twice a day on days 1-14 of each cycle.<br>* Other names: TGF-β receptor inhibitor;|
| Experimental: Arm 2: Enzalutamide alone<br> | Drug: Enzalutamide<br>* 160mg of enzalutamide is administered orally once a day on days 1-28 of each cycle.<br>* Other names: XTANDI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic castration-resistant prostate cancer, enzalutamide, LY2157299, TGF-β receptor inhibitor