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)

Phase 3Active Not RecruitingNCT05288166

Eli Lilly and Company925 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

925

Conditions

Prostatic Neoplasms Neoplasm Metastasis Urogenital Neoplasms Physiological Effects of Drugs Antineoplastic Agents Antineoplastic Agents, Hormonal

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Radiographic Progression-Free Survival (rPFS) Assessed by Investigator

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.

Time frame: From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 months)

Secondary Outcomes

Radiographic Progression-Free Survival (rPFS) Assessed by Blinded Independent Central Review (BICR)

Time frame: From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (up to 22 months)

Castration-resistant Prostate Cancer (CRPC)-Free Survival

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.

Time frame: 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)

Overall Survival (OS)

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 frame: From Date of Randomization to Date of Death Due to Any Cause (Up to 22 Months)

Time to Pain Progression

Time frame: 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

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 frame: 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) Measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) - Prostate Cancer Subscale

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.

Time frame: Randomization to the date of the first clinically meaningful HRQoL deterioration (up to 22 months)

Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib

Maximum plasma concentration at steady state (Cmax,ss) of abemaciclib was evaluated.

Time frame: Predose on Cycle 1 Day 1, Predose and Predose on Cycle 2 Day 1 and Predose on Cycle 3 Day 1 (28 Day Cycles)