A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to learn whether adding abemaciclib to abiraterone plus prednisone prolongs the time before prostate cancer gets worse. Participation may last approximately 60 months.

Official Title
-----------------
CYCLONE 3: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Abemaciclib in Combination With Abiraterone Plus Prednisone in Men With High-Risk Metastatic Hormone-Sensitive Prostate Cancer

Conditions
-----------------
Abiraterone Acetate, Prostatic Neoplasms, Neoplasm Metastasis, Urogenital Neoplasms, Physiological Effects of Drugs, Antineoplastic Agents, Antineoplastic Agents, Hormonal, Androgens, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Steroid Synthesis Inhibitors, Cytochrome P-450, Enzyme Inhibitors, Prednisone, Prednisolone, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6

Intervention / Treatment
-----------------
* Drug: Abemaciclib
* Drug: Abiraterone
* Drug: Prednisone or Prednisolone
* Drug: Placebo for Abemaciclib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adenocarcinoma of the prostate (as the predominant histology) High-risk metastatic hormone-sensitive prostate cancer. High risk is defined as: Greater than or equal to (≥)4 bone metastases by bone scan and/or ≥1 visceral metastases by computed tomography or magnetic resonance imaging Must have initiated androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or bilateral orchiectomy prior to randomization. Up to 3 months of ADT prior to randomization is permitted with or without first-generation anti-androgen. Adequate organ function Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Prior treatment with abemaciclib or any other cyclin dependent kinase 4 and 6 (CDK4 & 6) inhibitor Development of metastatic prostate cancer in the context of castrate levels of testosterone Received any prior systemic therapy for metastatic prostate cancer (including investigational agents), except for ADT and first-generation anti-androgen Clinically significant cardiovascular disease as evidenced by myocardial infarction, arterial thrombotic events, or severe/unstable angina in the past 6 months, or New York Heart Association Class II to IV heart failure History of syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin, or sudden cardiac arrest. Chronic and hemodynamically stable atrial arrhythmia well-controlled on medical therapy is permitted Uncontrolled hypertension Clinically active or chronic liver disease, moderate/severe hepatic impairment Known untreated central nervous system (CNS) metastasis. Participants with a history of treated brain metastases are eligible if stable for at least 8 weeks prior to randomization and off corticosteroid for at least 2 weeks prior to randomization

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abemaciclib + Abiraterone + Prednisone/Prednisolone<br>Abemaciclib plus (+) abiraterone + prednisone/prednisolone administered orally. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;Drug: Abiraterone<br>* Administered orally.<br>Drug: Prednisone or Prednisolone<br>* Administered orally.<br>|
| Active Comparator: Placebo + Abiraterone + Prednisone/Prednisolone<br>Placebo + abiraterone + prednisone/prednisolone administered orally. | Drug: Abiraterone<br>* Administered orally.<br>Drug: Prednisone or Prednisolone<br>* Administered orally.<br>Drug: Placebo for Abemaciclib<br>* Administered orally.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression-Free Survival (rPFS) Assessed by Investigator | rPFS Assessed by Investigator | Randomization to radiographic progression or death from any cause (approximately 48 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rPFS Assessed by Blinded Independent Central Review (BICR) | rPFS Assessed by BICR | Randomization to radiographic progression or death from any cause (approximately 48 months) | 
| Castration-resistant Prostate Cancer (CRPC)-free Survival | CRPC-free Survival | Randomization to the earliest date of PSA or radiographic progression with a testosterone level of ≤50 nanogram/deciliter (ng/dL); or death from any cause (approximately 48 months) | 
| Overall Survival (OS) | OS | Baseline to date of death due to any cause (approximately 60 months) | 
| Time to Pain Progression | Measured by a combination of 2 scales, the Brief Pain Inventory Short Form (BPI-SF) Worst Pain Numeric Rating Scale (NRS) and the Analgesic Quantification Algorithm (AQA) scale. The BPI-SF Worst Pain NRS is a self-reported 11-item questionnaire on worst pain intensity on the past 24 hours. Score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). The AQA scores analgesic use from 0 (minimum) to 7 (maximum). | Randomization to pain progression (approximately 48 months) | 
| Time to Deterioration in Health-Related Quality of Life (HRQoL) | Measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P; Physical well-being and Prostate Cancer Subscale). The FACT-P is a 39-item self-reported questionnaire that assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better quality of life. | Randomization to the date of HRQoL deterioration (approximately 48 Months) | 
| Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | PK: Mean steady state exposure of abemaciclib | Postdose Cycle 1 Day 1 through Predose Cycle 3 Day 1 (28 Day Cycles) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mHSPC, Metastatic Hormone Sensitive Prostate Cancer, Stage IV Prostate Cancer, Recurrent Prostate Cancer, De Novo Metastatic Prostate Cancer, High-Risk, Visceral metastasis, Cyclin-Dependent Kinase 4 (CDK4), Cyclin-Dependent Kinase 6 (CDK6), CDK4, CDK6, CDK4/6