A Study of Abiraterone Acetate Plus Prednisone with or without Abemaciclib in Patients with Metastatic Castration-Resistant Prostate Cancer

INTERVENTION: Product Name: abemaciclib Product Code: LY2835219 Pharmaceutical Form: Capsule, hard INN or Proposed INN: abemaciclib Current Sponsor code: LY2835219 Other descriptive name: ABEMACICLIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Metastatic Castration‐Resistant Prostate Cancer ; MedDRA version: 20.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 20.0 Level: LLT Classification code 10076506 Term: Castration‐resistant prostate cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Part 1: To determine the RP2D of abemaciclib that may be safely administered to patients with mCRPC in combination with abiaterone acetate and prednisone.; Part 1&2:; To compare the rPFS of patients receiving abiraterone acetate plus prednisone with or without abemaciclib. ; To compare the time to PSA progression in patients receiving abiraterone acetate plus prednisone with or without abemaciclib. ; ; Primary end point(s): Part 1: Safety (including but not limited to): TEAEs, SAEs, deaths, and clinical laboratory abnormalities; Part 1 & 2: rPFS; Time to PSA progression ; Secondary Objective: To characterize further the safety profile of the combination of abemaciclib and abiraterone acetate plus prednisone.; To compare the efficacy in patients receiving abiraterone acetate plus prednisone with or without abemaciclib. ; Time to Symptomatic Progression; To characterize the PK of abemaciclib and abiraterone acetate when administered in combination; Timepoint(s) of evaluation of this end point: Safety evaluations will occur at each study visit.; Radiologic assessment every 8 weeks for the first 24 weeks, every 12 weeks thereafter, and within 14 days of symptomatic progression if no radiographic progression yet.; SECONDARY OUTCOME: Secondary end point(s): The safety endpoints evaluated will include but are not limited to the following: AEs, TEAEs, SAEs, clinical laboratory tests, ECGs, vital signs, and physical examinations. ; • ORR and DoR ; • OS ; Time from randomization to any of the following (whichever occurs earlier): ; ‐ Symptomatic Skeletal Event (SSE) ; ‐ Pain progression or worsening of disease‐related symptoms requiring initiation of a new systemic anti‐cancer therapy ; ‐ Development of clinically significant symptoms due to loco‐regional tumor progression requiring surgical intervention or radiation therapy ; Abemaciclib and abiraterone acetate steady state plasma concentrations. ; Timepoint(s) of evaluation of this end point: Safety evaluations will occur at each study visit. ; Radiologic assessment every 8 weeks for the first 24 weeks, every 12 weeks thereafter, and within 14 days of symptomatic progression if no radiographic progression yet. ; INCLUSION CRITERIA: [1] Male patients, 18 years of age or greater; willing and able to provide written informed consent. [2] Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology. [5] Progressive disease at study entry demonstrated during continuous androgen deprivation therapy (ADT)/post orchiectomy defined as one or more of the following criteria: †[3] Metastatic prostate cancer documented by positive bone scan and/or measurable soft tissue metastatic lesions by computed tomography (CT) or magnetic resonance imaging (MRI). If lymph node metastasis is the only evidence of metastasis, it must be =1.5cm in the short axis. Visceral metastasis, including to liver, is allowed. [4] Serum testosterone level = 1.73 nmol/L (50 ng/dL) at the Screening visit. Patients who have not undergone orchiectomy are required to continue androgen‐deprivation therapy (LHRH agonists/antagonists) throughout the study.