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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Recruiting

CT.gov ID

NCT02452008

Collaborator

Eli Lilly and Company (Industry)

Enrollment

Locations

Arms

90.9

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Enzalutamide Drug: LY2157299	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 3, 2016

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Enzalutamide with LY2157299	Drug: Enzalutamide 160mg of enzalutamide is administered orally once a day on days 1-28 of each cycle. Other Names: XTANDI Drug: LY2157299 150 mg of LY2157299 is administered orally twice a day on days 1-14 of each cycle. Other Names: TGF-β receptor inhibitor
Experimental: Arm 2: Enzalutamide alone	Drug: Enzalutamide 160mg of enzalutamide is administered orally once a day on days 1-28 of each cycle. Other Names: XTANDI

Arm

Intervention/Treatment

Experimental: Arm 1: Enzalutamide with LY2157299

Drug: Enzalutamide

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

Other Names:

XTANDI

Drug: LY2157299

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

Other Names:

TGF-β receptor inhibitor

Experimental: Arm 2: Enzalutamide alone

Drug: Enzalutamide

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

Other Names:

XTANDI

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
2	Northwestern University	Chicago	Illinois	United States	60611
3	University of Chicago	Chicago	Illinois	United States	60637
4	Johns Hopkins University	Baltimore	Maryland	United States	21205