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Abemaciclib (LY2835219) in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer (CYCLONE 1)

Primary Purpose

Metastatic Castration-Resistant Prostate Cancer

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Abemaciclib
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Castration-Resistant Prostate Cancer focused on measuring mCRPC, CDK4, CDK6, CDK4/6, CDK4&6 inhibitor, CDK4/6 inhibitor, LY2835219, CYCLONE 1, CYCLONE1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Utah - Huntsman Cancer Institute
  • Seattle Cancer Care Alliance
  • Centre Leon Berard
  • Institut Paoli-Calmettes
  • Hopital Europeen Georges Pompidou
  • Institut Claudius Regaud
  • Gustave Roussy
  • Institut Catala d'Oncologia
  • Corporacion Sanitaria Parc Tauli
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Universitari Vall d'Hebron
  • Hospital General Universitario Gregorio Maranon
  • Hospital Universitario Ramon y Cajal
  • Hospital Universitario 12 de Octubre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

200 milligram (mg) Abemaciclib Twice Daily

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib
PK: Cmax,ss of abemaciclib is reported.
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib
PK: Cmin,ss of abemaciclib is reported.
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.
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.
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.

Full Information

First Posted
May 28, 2020
Last Updated
April 27, 2023
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT04408924
Brief Title
Abemaciclib (LY2835219) in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer
Acronym
CYCLONE 1
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 1, 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 20, 2021 (Actual)
Primary Completion Date
April 27, 2022 (Actual)
Study Completion Date
August 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration-Resistant Prostate Cancer
Keywords
mCRPC, CDK4, CDK6, CDK4/6, CDK4&6 inhibitor, CDK4/6 inhibitor, LY2835219, CYCLONE 1, CYCLONE1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
200 milligram (mg) Abemaciclib Twice Daily
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Abemaciclib
Other Intervention Name(s)
LY2835219
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Percentage of Participants With Confirmed Objective Response (Objective Response Rate [ORR])
Description
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.
Time Frame
From Date of First Dose until Objective Progression (Up To 12.8 Months)
Secondary Outcome Measure Information:
Title
Radiographic Progression-Free Survival (rPFS)
Description
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.
Time Frame
From Date of First Dose until Objective Progression or Death from Any Cause (Up To 12.8 Months)
Title
Overall Survival (OS)
Description
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.
Time Frame
From Date of First Dose until Date of Death from Any Cause (Estimated Up To 28 Months)
Title
Duration of Response (DoR)
Description
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.
Time Frame
CR or PR to Disease Progression or Death Due to Any Cause (Estimated Up to 28 Months)
Title
Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])
Description
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.
Time Frame
From Date of First Dose until Measured Progressive Disease or Death Due to Any Cause (Up To 12.8 Months)
Title
Time to Prostate-Specific Antigen (PSA) Progression
Description
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.
Time Frame
From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months)
Title
Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response (PSA Response Rate)
Description
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.
Time Frame
From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months)
Title
Time to Symptomatic Progression
Description
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.
Time Frame
From Date of First Dose until Symptomatic Progression (Up to 12.8 Months)
Title
Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib
Description
PK: Cmax,ss of abemaciclib is reported.
Time Frame
Cycle (C) 1 Day (D) 1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose
Title
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib
Description
PK: Cmin,ss of abemaciclib is reported.
Time Frame
C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose
Title
PK: Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib Metabolites (Total Active Species)
Description
PK: Cmax,ss of abemaciclib metabolites (Total Active Species) is reported.
Time Frame
C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose
Title
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib Metabolites (Total Active Species)
Description
PK: Cmin,ss of abemaciclib metabolites (Total Active Species) is reported.
Time Frame
C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose
Title
Baseline Ki-67 Expression by Immunohistochemistry (IHC)
Description
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 Frame
Baseline

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
University of Utah - Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Centre Leon Berard
City
Lyon Cedex 08
ZIP/Postal Code
69373
Country
France
Facility Name
Institut Paoli-Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Hopital Europeen Georges Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Gustave Roussy
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Institut Catala d'Oncologia
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Corporacion Sanitaria Parc Tauli
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital General Universitario Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
https://vivli.org/
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/5ARvCmtBk1XeifKLCEUPWB
Description
Abemaciclib (LY2835219) in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer (CYCLONE 1)

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

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