Abemaciclib (LY2835219) in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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The study will evaluate how safe and effective abemaciclib is when given to participants whose metastatic prostate cancer progresses after they had received several previous treatments.

Official Title
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CYCLONE 1: A Phase 2 Study of Abemaciclib in Metastatic Castration-Resistant Prostate Cancer Patients Previously Treated With a Novel Hormonal Agent and Taxane-based Chemotherapy

Conditions
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Metastatic Castration-Resistant Prostate Cancer

Intervention / Treatment
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* Drug: Abemaciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have metastatic prostate cancer for which castration (medical or surgical) is no longer effective (castration-resistant). Participant must have disease spread to soft tissue that is measurable. Participant must have documented evidence of progressive disease by PSA test or imaging. Participant must have previously received at least one of the following treatment: abiraterone acetate, apalutamide, darolutamide or enzalutamide. Participant must have previously received chemotherapy with docetaxel and cabazitaxel. Participant must be willing and amenable to undergo a biopsy of tumor tissue (or able to provide adequate archived tumor tissue sample) and to provide blood for research. Participant must have good physical functioning ability and adequate organ function. Exclusion Criteria: Participant must not have received more than 3 therapy regimens for metastatic castration-resistant prostate cancer (NOTE: GnRHa, first-generation antiandrogens (flutamide, nilutamide, or bicalutamide), diethylstilbestrol (DES) (or other estrogens), corticosteroids, ketoconazole, and bone loss-prevention will not count as systemic therapy regimens. Participants must not have previously received abemaciclib or any cyclin-dependent kinase (CDK)4 and/or CDK6 inhibitors. Participants must not have serious and/or uncontrolled preexisting medical condition(s) including but not limited to severe renal impairment, severe hepatic impairment, interstitial lung disease (ILD)/pneumonitis, severe dyspnea at rest or requiring oxygen therapy or other serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. Participants must not have, or suspected to have, brain metastasis. Participants must not have untreated spinal cord compression, evidence of spinal metastases with risk of spinal compression or structurally unstable bone lesions suggesting impending fracture.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 200 milligram (mg) Abemaciclib Twice Daily<br>Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Confirmed Objective Response (Objective Response Rate [ORR]) | ORR is defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) in soft tissue per response evaluation criteria in solid tumors (RECIST) version 1.1 and do not have concurrent bone progression per Prostate Cancer Clinical Trials Working Group 3 (PCWG3), as assessed by the investigator. ORR = (participants with confirmed CR and no bone progression) + (participants with confirmed PR and no bone progression) x 100 / all treated participants. | From Date of First Dose until Objective Progression (Up To 12.8 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression-Free Survival (rPFS) | The rPFS time is measured from the date of first dose to the earliest date of investigator-assessed radiographic progression per RECIST 1.1 for soft tissue and PCWG3 criteria for bone, or death from any cause, whichever occurred first. Participants who have neither progressed nor died will be censored at the day of their last radiographic tumor assessment (if available) or date of first dose if no post initiation (i.e., postbaseline) radiographic assessment is available. | From Date of First Dose until Objective Progression or Death from Any Cause (Up To 12.8 Months) | 
| Overall Survival (OS) | OS time is measured from the date of first dose 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. | From Date of First Dose until Date of Death from Any Cause (Estimated Up To 28 Months) | 
| Duration of Response (DoR) | DoR is measured only for confirmed responders (participants with a confirmed soft tissue best overall response of CR or PR per RECIST 1.1 no concurrent bone progression per PCWG3. It is measured from the date of first evidence of soft tissue CR or PR to the earliest date of investigator-assessed radiographic progression or death from any cause, whichever is earlier. | CR or PR to Disease Progression or Death Due to Any Cause (Estimated Up to 28 Months) | 
| Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR]) | The DCR is defined as the percentage of participants with confirmed soft tissue best overall response of CR, PR, or stable disease (SD) per RECIST 1.1, and do not have concurrent bone disease progression per PCWG3. | From Date of First Dose until Measured Progressive Disease or Death Due to Any Cause (Up To 12.8 Months) | 
| Time to Prostate-Specific Antigen (PSA) Progression | Time to PSA progression is defined as the time from the date of treatment initiation to the date of first observation of PSA progression. 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. | From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months) | 
| Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response (PSA Response Rate) | The PSA response rate is defined as the percentage of participants with a reduction in PSA level ≥50% from baseline, confirmed with a second assessment conducted at least 3 weeks later. | From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months) | 
| Time to Symptomatic Progression | Time to symptomatic progression is defined as the time from first dose to any of the following (whichever occurred earlier): 1) symptomatic skeletal event, 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 anticancer therapy; and 3) development of clinically significant symptoms due to locoregional tumor progression requiring surgical intervention or radiation therapy. For participants who were not known to have symptomatic progression at the time of data analysis, data were censored on the last date at which no symptomatic progression was indicated. | From Date of First Dose until Symptomatic Progression (Up to 12.8 Months) | 
| Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | PK: Cmax,ss of abemaciclib is reported. | Cycle (C) 1 Day (D) 1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose | 
| PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib | PK: Cmin,ss of abemaciclib is reported. | C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose | 
| PK: Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib Metabolites (Total Active Species) | PK: Cmax,ss of abemaciclib metabolites (Total Active Species) is reported. | C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose | 
| PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib Metabolites (Total Active Species) | PK: Cmin,ss of abemaciclib metabolites (Total Active Species) is reported. | C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose | 
| Baseline Ki-67 Expression by Immunohistochemistry (IHC) | Percentage of participants with expression of Ki-67 proliferation marker at baseline by immunohistochemistry. Baseline expression of the Ki-67 proliferation marker was evaluated by IHC utilizing a 20% or higher score to define high Ki-67 expression. The percentage of Ki-67 positive cells was defined by the number of non-apoptotic tumor cells with unequivocal brown nuclear staining (intensities ≥1 using a 0-3 scale) over the total number of non-apoptotic tumor cells. Unit of Measure is percentage of participants with low or high baseline Ki-67 expression. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mCRPC, CDK4, CDK6, CDK4/6, CDK4&6 inhibitor, CDK4/6 inhibitor, LY2835219, CYCLONE 1, CYCLONE1