A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer

Study Overview
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Brief Summary
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This study is being done to see how safe and effective abemaciclib is when given together with abiraterone acetate plus prednisone in participants with metastatic castration resistant prostate cancer. Prednisolone may be used instead of prednisone per local regulation.

Official Title
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A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib in Patients With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Abemaciclib
* Drug: Abiraterone Acetate
* Drug: Prednisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate. Metastatic prostate cancer documented by positive bone scan and/or measurable soft tissue metastatic lesions by CT or magnetic resonance imaging (MRI). Progressive disease at study entry demonstrated during continuous androgen-deprivation therapy (ADT)/post orchiectomy defined as one or more of the following: PSA progression Radiographic progression per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 for soft tissue and/or per Prostate Cancer Working Group 3 (PCWG3) for bone, with or without PSA progression Have adequate organ function. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. Exclusion Criteria: Prior therapy with cytochrome P450 (CYP)17 inhibitors. Prior treatment with abemaciclib or any cyclin-dependent kinase (CDK) 4 & 6 inhibitors. Prior cytotoxic chemotherapy for metastatic castration resistant prostate cancer (participants treated with docetaxel in the metastatic hormone-sensitive prostate cancer [mHSPC] are eligible). Prior radiopharmaceuticals for prostate cancer, or prior enzalutamide, apalutamide, darolutamide or sipuleucel-T. Participants who had prior radiation or surgery to all target lesions. Currently enrolled in a clinical study involving an investigational product. Gastrointestinal disorder affecting the absorption or ability to swallow large pills. Clinically significant heart disease, active or chronic liver disease, moderate/severe hepatic impairment (Child-Pugh Class B and C).

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1. Abiraterone plus Prednisone and Abemaciclib<br>Abiraterone plus prednisone administered orally and abemaciclib administered orally. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;Drug: Abiraterone Acetate<br>* Administered orally.<br>Drug: Prednisone<br>* Administered orally.<br>|
| Experimental: A2. Abiraterone plus Prednisone and Abemaciclib<br>Abiraterone plus prednisone administered orally and abemaciclib administered orally. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;Drug: Abiraterone Acetate<br>* Administered orally.<br>Drug: Prednisone<br>* Administered orally.<br>|
| Active Comparator: B1. Abiraterone plus Prednisone and Placebo<br>Abiraterone plus prednisone administered orally and placebo administered orally. | Drug: Abiraterone Acetate<br>* Administered orally.<br>Drug: Prednisone<br>* Administered orally.<br>Drug: Placebo<br>* Administered orally.<br>|
| Active Comparator: B2. Abiraterone plus Prednisone and Placebo<br>Abiraterone plus prednisone administered orally and placebo administered orally. | Drug: Abiraterone Acetate<br>* Administered orally.<br>Drug: Prednisone<br>* Administered orally.<br>Drug: Placebo<br>* Administered orally.<br>|
| Experimental: A. Abiraterone plus Prednisone and Abemaciclib<br>Abiraterone plus prednisone administered orally and abemaciclib administered orally. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;Drug: Abiraterone Acetate<br>* Administered orally.<br>Drug: Prednisone<br>* Administered orally.<br>|
| Active Comparator: B. Abiraterone plus Prednisone and Placebo<br>Abiraterone plus prednisone administered orally and placebo administered orally. | Drug: Abiraterone Acetate<br>* Administered orally.<br>Drug: Prednisone<br>* Administered orally.<br>Drug: Placebo<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression Free Survival (rPFS) | rPFS by investigator assessment | Baseline to Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Prostate-Specific Antigen (PSA) Progression | Time to PSA progression | Baseline to the Date of the First Observation of PSA Progression (Estimated up to 21 Months) | 
| Radiographic Progression Free Survival (rPFS) | rPFS by blinded, independent, central review | Baseline to Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months) | 
| Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR) | ORR: Percentage of participants with a CR or PR | Baseline to Radiographic Disease Progression (Estimated up to 21 Months) | 
| Duration of Response (DOR) | DOR | Date of First Documented CR or PR to Date of Radiographic Disease Progression or Death from Any Cause (Estimated up to 21 Months) | 
| Overall Survival (OS) | OS | Baseline to Date of Death Due to Any Cause (Estimated up to 40 Months) | 
| Time to Symptomatic Progression | Time to symptomatic progression | Baseline to the Date of the First Documented Symptomatic Progression (Estimated up to 21 Months) | 
| Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | PK: Mean steady state exposure of abemaciclib | Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) | 
| PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | PK: Mean steady state exposure of abemaciclib metabolite LSN2839567 | Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) | 
| PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | PK: Mean steady state exposure of abemaciclib metabolite LSN3106726 | Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) | 
| PK: Mean Steady State Exposure of Abiraterone Acetate | PK: Mean Steady State Exposure of Abiraterone Acetate | Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) | 
| Time to Worst Pain Progression | Measured by the Worst Pain Numeric Rating Scale (NRS) and World Health Organization-Analgesic Ladder (WHO-AL). NRS score measures worst pain over the last 24 hours on a 0 to 10-point NRS, where 0 -s no pain and 10 is pain as bad as you can imagine. The WHO-AL classifies analgesic use into four categories, where 1 = no analgesic and 4 = strong opioids. | Baseline through follow-up (Estimated up to 21 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Castration Resistant Prostate Cancer, mCRPC