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

Phase 2

Active, not recruiting

• Conditions: Prostate Cancer
• Interventions: Drug: Abemaciclib; Drug: Placebo; Drug: Abiraterone acetate; Drug: Prednisone

• Registration Number: NCT03706365
• Lead Sponsor: Eli Lilly and Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-18
• Study First Submitted QC: 2018-10-11
• Study First Posted: 2018-10-16
• Study Start: 2018-11-26
• Primary Completion: 2024-01-02
• Results First Submitted: 2024-12-31
• Results First Submitted QC: 2025-02-28
• Results First Posted: 2025-03-06
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-20
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 393

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Abemaciclib	Abemaciclib	Participants received 200 milligrams (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg 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 acetate	Participants received 200 milligrams (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg 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	Participants received 200 milligrams (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg 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	Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg 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 acetate	Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg 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	Participants received placebo BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg 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)	From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (Up to 60 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
Time to Prostate-Specific Antigen (PSA) Progression	From Date of Randomization to the Date of the First Observation of PSA Progression (Up to 60 Months)	The PSA progression is defined as a greater than or equal to (\>=) 25 percentage (%) increase and an absolute increase of \>=2 nanogram/milliliter (ng/mL) above the nadir (or baseline value if baseline is the smallest on study), which is confirmed by a second value obtained 3 or more weeks later.
Radiographic Progression Free Survival (rPFS) Determined by Blinded Independent Central Review	From Date of Randomization Until Radiographic Disease Progression or Death from Any Cause (Up to 60 Months)	rPFS is defined as the time from the date of randomization to the earliest date of radiographic disease progression determined by blinded independent central review (BICR) or death from any cause, whichever occurs first.
Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)	Baseline to Radiographic Disease Progression (Up to 60 Months)	ORR is a summary measure of best overall response (BOR) as defined by RECIST 1.1 for soft tissue per investigator assessment. BOR is derived from time point responses. All time point responses observed while on study treatment and during the short-term follow-up period (but before the initiation of post-discontinuation systemic anticancer therapy) will be included in the derivation.; Each patient's BOR will be categorized as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). A BOR of CR or PR will require confirmation, but sensitivity analyses of response-based endpoints may be performed where confirmation of a BOR of CR or PR is not required.
Duration of Response (DOR)	Date of First Documented CR or PR to Date of Radiographic Disease Progression or Death from Any Cause (Up to 60 Months)	The DoR time is defined only for responders (participants with a soft tissue BOR of CR or PR) in the measurable disease population. It is measured from the date of first evidence of soft tissue CR or PR to the earliest date of investigator determined radiographic disease progression or death from any cause, whichever is earlier.
Overall Survival (OS)	From Date of Randomization to Date of Death Due to Any Cause (Up to 60 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 Symptomatic Progression	From Randomization to the Date of the First Documented Symptomatic Progression (Up to 60 Months)	Time to symptomatic progression is defined as the time from randomization to any of the following (whichever occurs earlier): 1. Symptomatic Skeletal Event (SSE), defined as symptomatic fracture, surgery or radiation to bone, or spinal cord compression.; 2. Pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy.; 3. Development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy.
Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib	Cycle (C) 1 Day (D) 1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle)	PK: Mean steady state exposure of abemaciclib.
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567	C1 D1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle)	PK: Mean steady state exposure of abemaciclib metabolite LSN2839567.
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726	C1 D1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle)	PK: Mean steady state exposure of abemaciclib metabolite LSN3106726.
Time to Worst Pain Progression	From Randomization Through Follow-up (Up to 60 months)	Time to Worst Pain Progression defined as the time from randomization to any of the following (whichever occurs earlier): For participants without opioid use at baseline (World Health Organization-Analgesic Ladder-WHO-AL ≤ 2):- Worst pain progression (an increase of 2 points from baseline on the Worst Pain Numeric Rating Scale (NRS) item on 2 consecutive evaluations), Initiation of weak or strong opioids (WHO-AL ≥ 3); For participants with weak or strong opioid use at baseline (WHO-AL ≥ 3): Worst pain progression (an increase of 2 points from baseline on the Worst Pain NRS item on 2 consecutive evaluations) without concurrent decreased opioid use (a decrease in WHO-AL of 1 or more) -Increased opioid use (an increase in WHO-AL of 1 or more).
PK: Mean Steady State Exposure of Abiraterone Acetate	C1 D15, Post dose	PK: Mean Steady State Exposure of Abiraterone Acetate.

Trial Locations

Locations (110)

St. Joseph's Hospital and Medical Center; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic in Arizona - Phoenix; 🇺🇸 Phoenix, Arizona, United States

The University of Arizona Cancer Center - North Campus; 🇺🇸 Tucson, Arizona, United States

St. Bernards Medical Center; 🇺🇸 Jonesboro, Arkansas, United States

CBCC Global Research, Inc.; 🇺🇸 Bakersfield, California, United States

Providence St. Jude Medical Center; 🇺🇸 Fullerton, California, United States

Moores Cancer Center; 🇺🇸 La Jolla, California, United States

TRIO-US (Translational Research in Oncology-US); 🇺🇸 Los Angeles, California, United States

UCLA Hematology/Oncology - Westwood (Building 100); 🇺🇸 Los Angeles, California, United States

Pacific Cancer Care; 🇺🇸 Monterey, California, United States

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