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)

Not Applicable

Active, not recruiting

Conditions: Prostatic Neoplasms
Neoplasm Metastasis
Urogenital Neoplasms
Physiological Effects of Drugs
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Abiraterone Acetate

Interventions: Drug: Abemaciclib
Drug: Abiraterone
Drug: Prednisone or Prednisolone
Drug: Placebo for Abemaciclib

Registration Number: NCT05288166

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Male

Target Recruitment: 925

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Abemaciclib	Abemaciclib	Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Abemaciclib	Abiraterone	Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Abemaciclib	Prednisone or Prednisolone	Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Placebo	Abiraterone	Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Placebo	Prednisone or Prednisolone	Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Placebo	Placebo for Abemaciclib	Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.

Primary Outcome Measures

Name	Time	Method
Radiographic Progression-Free Survival (rPFS) Assessed by Investigator	From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 months)	The rPFS time is measured from the date of randomization to the earliest date of investigator determined radiographic disease progression (by objective radiographic disease assessment per response evaluation criteria in solid tumors (RECIST) version 1.1 for soft tissue AND/OR radionuclide bone scan using prostate cancer working group 3 -PCWG3 criteria for bone) or death from any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Radiographic Progression-Free Survival (rPFS) Assessed by Blinded Independent Central Review (BICR)	From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 months)	The rPFS time is measured from the date of randomization to the earliest date of investigator determined radiographic disease progression (by objective radiographic disease assessment per response evaluation criteria in solid tumors (RECIST) version 1.1 for soft tissue AND/OR radionuclide bone scan using prostate cancer working group 3 -PCWG3 criteria for bone) or death from any cause, whichever occurs first.
Castration-resistant Prostate Cancer (CRPC)-Free Survival	Randomization to the earliest date of PSA or radiographic progression with a testosterone level of ≤50 ng/dL; or death from any cause (up to 22 months)	CRPC-free survival is defined as the time from the date of randomization to the earliest date of castration resistance, as demonstrated by any of the following (whichever occurs earliest): Confirmed prostate-specific antigen (PSA) progression with serum testosterone ≤50 nanogram/deciliter (ng/dL) (≤1.73 nanomoles per liter(nmol/L)). Investigator-assessed radiographic progression with serum testosterone ≤50 ng/dL (≤1.73 nmol/L). Death from any cause.
Overall Survival (OS)	From Date of Randomization to Date of Death Due to Any Cause (Up to 22 Months)	The OS time is measured from the date of randomization to the date of death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data were censored on the last date the participant was known to be alive.
Time to Pain Progression	Randomization to pain progression (up to 22 months)
Time to Deterioration in Health-Related Quality of Life (HRQoL) Measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) - Physical Well-Being Subscale	Randomization to the date of the first clinically meaningful HRQoL deterioration (up to 22 months)	Time to deterioration in health-related quality of life (HRQoL) was defined as the time from randomization to the date of the first clinically meaningful HRQoL deterioration on 2 consecutive measurements. HRQoL evaluation was performed using the FACT-P questionnaire. Physical Well-Being subscale is a subsection of FACT-P questionnaire. FACT-P consists of 39 core items to assess health related quality of life in participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate cancer subscale (12 items). Each item is rated from 0 (Not at all) to 4 (Very much) and combined to produce subscale scores. FACT-P total score was the sum of all 5 subscale scores. It ranged from 0 to 156 with higher score indicating better quality of life. Physical well-being subscale score ranges from 0 to 28 with high score indicating better quality of life.
Time to Deterioration in Health-Related Quality of Life (HRQoL) Measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) - Prostate Cancer Subscale	Randomization to the date of the first clinically meaningful HRQoL deterioration (up to 22 months)	Time to deterioration in health-related quality of life (HRQoL) was defined as the time from randomization to the date of the first clinically meaningful HRQoL deterioration on 2 consecutive measurements. HRQoL evaluation was performed using the FACT-P questionnaire. Prostate Cancer Subscale is a subsection of FACT-P questionnaire. FACT-P consists of 39 core items to assess health related quality of life in participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate cancer subscale (12 items). Each item is rated from 0 (Not at all) to 4 (Very much) and combined to produce subscale scores. FACT-P total score was the sum of all 5 subscale scores. It ranged from 0 to 156 with higher score indicating better quality of life. Prostate cancer subscale score ranges from 0 to 48 with high score indicating better quality of life.
Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib	Predose on Cycle 1 Day 1, Predose and Predose on Cycle 2 Day 1 and Predose on Cycle 3 Day 1 (28 Day Cycles)	Maximum plasma concentration at steady state (Cmax,ss) of abemaciclib was evaluated.

Trial Locations

Locations (263): Arizona Oncology Associates, P.C. - HOPE
🇺🇸
Prescott, Arizona, United States
The University of Arizona Cancer Center - North Campus
🇺🇸
Tucson, Arizona, United States
Genesis Cancer and Blood Institute
🇺🇸
Hot Springs, Arkansas, United States
St. Bernards Medical Center
🇺🇸
Jonesboro, Arkansas, United States
Highlands Oncology Group
🇺🇸
Springdale, Arkansas, United States
Orange Coast Memorial Medical Center
🇺🇸
Fountain Valley, California, United States
Providence Medical Foundation
🇺🇸
Fullerton, California, United States
Moores Cancer Center
🇺🇸
La Jolla, California, United States
MemorialCare Health System - Long Beach Medical Center
🇺🇸
Long Beach, California, United States
Cancer and Blood Specialty Clinic
🇺🇸
Los Alamitos, California, United States
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Arizona Oncology Associates, P.C. - HOPE
🇺🇸Prescott, Arizona, United States