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
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Eli Lilly and Company
- Enrollment
- 393
- Locations
- 112
- Primary Endpoint
- Radiographic Progression Free Survival (rPFS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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).
Arms & Interventions
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.
Intervention: Abiraterone acetate (Drug)
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.
Intervention: Abiraterone acetate (Drug)
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.
Intervention: Prednisone (Drug)
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.
Intervention: Prednisone (Drug)
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.
Intervention: Abemaciclib (Drug)
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Radiographic Progression Free Survival (rPFS)
Time Frame: 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 Outcomes
- 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))
- 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))
- 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))
- 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))
- Overall Survival (OS)(From Date of Randomization to Date of Death Due to Any Cause (Up to 60 Months))
- Time to Symptomatic Progression(From Randomization to the Date of the First Documented Symptomatic Progression (Up to 60 Months))
- 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 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 LSN3106726(C1 D1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle))
- Time to Worst Pain Progression(From Randomization Through Follow-up (Up to 60 months))
- PK: Mean Steady State Exposure of Abiraterone Acetate(C1 D15, Post dose)