SHS_492273 ZHAS CELI 15052

A Double-Blinded, Placebo-Controlled, Randomized Phase II Study of Enzalutamide With or Without the PI3 Kinase/mTOR Inhibitor LY3023414 in Men with Metastatic Castration Resistant Prostate Cancer

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY3023414 in combination with enzalutamide in men with prostate cancer.

Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the prostate. Documented metastatic disease. Prostate cancer progression documented by PSA and/or radiographic progression according to prostate cancer working group 2 (PCWG2). Prior abiraterone treatment completed at least 4 weeks prior to cycle 1 day 1. Surgically or medically castrated, with testosterone levels of < 50 nanograms/deciliter. ECOG Performance status of 0 or 1. Ability to swallow the study drugs whole. Adequate hematologic function. Adequate coagulation parameters. Availability of tumor tissue from any time since diagnosis of prostate cancer disease. If no tumor samples are available the participant might still be eligible.

Exclusion Criteria:
Prior cytotoxic chemotherapy, immunotherapy, PI3K/AKT/mTOR agent, or RA 223 dichloride for treatment of CRPC. Docetaxel okay in the hormone-sensitive setting. Prior investigational new generation potent anti-androgen therapy. Prior treatment with enzalutamide. Pathological finding consistent with small cell carcinoma of the prostate. Prior systemic treatment with an azole drug within 4 weeks of cycle 1 day 1. Known brain metastasis. History of (a) seizure or any condition that may predispose to seizure; or (b) loss of consciousness or transient ischemic attack within 12 months prior to day 1 of cycle 1. Uncontrolled hypertension. Serious pre-existing medical conditions. Known acute or chronic leukemia or current hematologic malignancies. Insulin-dependent diabetes mellitus; however, type 2 diabetes mellitus is okay if blood glucose level is controlled (hemoglobin A1c <7%). Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy. Have a history of New York Heart Association Class ?3, QTcF interval > 450 milliseconds on screening electrocardiogram, unstable angina, or myocardial infarction in 6 months prior to study drug administration. Clinically significant electrolyte imbalance ? grade 2. Current treatment with therapeutic doses of warfarin sodium. Have initiated treatment with bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents ?28 days prior to day 1, cycle 1. Concurrent serious infections requiring parenteral antibiotic therapy. Second primary malignancy that may affect the interpretation of results. Active, known fungal, bacterial, or viral infection.
Phase II
Cancer, All Other
Song Zhao, M.D.
Eli Lilly and Company
Andrew Bathan
  • Swedish Medical Center