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

Phase 2

Completed

Conditions: Metastatic Castration-Resistant Prostate Cancer

Interventions: Drug: Abemaciclib

Registration Number: NCT04408924

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 44

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
200 milligram (mg) Abemaciclib Twice Daily	Abemaciclib	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Confirmed Objective Response (Objective Response Rate [ORR])	From Date of First Dose until Objective Progression (Up To 12.8 Months)	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.

Secondary Outcome Measures

Name	Time	Method
Time to Prostate-Specific Antigen (PSA) Progression	From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months)	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.
Radiographic Progression-Free Survival (rPFS)	From Date of First Dose until Objective Progression or Death from Any Cause (Up To 12.8 Months)	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.
Overall Survival (OS)	From Date of First Dose until Date of Death from Any Cause (Up To 28 Months)	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.
Duration of Response (DoR)	CR or PR to Disease Progression or Death Due to Any Cause (Up to 12 Months)	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.
Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])	From Date of First Dose until Measured Progressive Disease or Death Due to Any Cause (Up To 12.8 Months)	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.
Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response (PSA Response Rate)	From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months)	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.
PK: Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib Metabolites (Total Active Species)	C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose	PK: Cmax,ss of abemaciclib metabolites (Total Active Species) is reported.
Percentage of Participants With Expression of Ki-67 Proliferation Marker by Immunohistochemistry (IHC)	Baseline	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.
Time to Symptomatic Progression	From Date of First Dose until Symptomatic Progression (Up to 12.8 Months)	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.
Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib	Cycle (C) 1 Day (D) 1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose	PK: Cmax,ss of abemaciclib is reported. The cycle length was 28 days.
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib	C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose	PK: Cmin,ss of abemaciclib is reported.
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib Metabolites (Total Active Species)	C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose	PK: Cmin,ss of abemaciclib metabolites (Total Active Species) is reported.

Trial Locations

Locations (14): Seattle Cancer Care Alliance
🇺🇸
Seattle, Washington, United States
Hopital Europeen Georges Pompidou
🇫🇷
Paris, France
University of Utah - Huntsman Cancer Institute
🇺🇸
Salt Lake City, Utah, United States
Institut Paoli-Calmettes
🇫🇷
Marseille, France
Gustave Roussy
🇫🇷
Villejuif Cedex, France
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Centre Leon Berard
🇫🇷
Lyon Cedex 08, France
Institut Claudius Regaud
🇫🇷
Toulouse cedex 9, France
Hospital Universitario Ramon y Cajal
🇪🇸
Madrid, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸
Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Corporacion Sanitaria Parc Tauli
🇪🇸
Sabadell, Barcelona, Spain
Institut Catala d'Oncologia
🇪🇸
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain