Clinical Trial Results:
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
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Summary
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EudraCT number |
2020-000290-24 |
Trial protocol |
FR |
Global end of trial date |
02 Jun 2023
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Results information
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Results version number |
v2(current) |
This version publication date |
15 Jun 2024
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First version publication date |
13 May 2023
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
I3Y-MC-JPCY
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04408924 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Trial Number: 17583 | ||
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Sponsors
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Sponsor organisation name |
Eli Lilly and Company
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Sponsor organisation address |
Lilly Corporate Center, Indianapolis, IN, United States, 46285
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Public contact |
Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
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Scientific contact |
Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Jun 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Jun 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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.
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Protection of trial subjects |
This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Jan 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 14
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Country: Number of subjects enrolled |
Spain: 27
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Country: Number of subjects enrolled |
United States: 3
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Worldwide total number of subjects |
44
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EEA total number of subjects |
41
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
14
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From 65 to 84 years |
29
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
Not Applicable | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Abemaciclib
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Investigational medicinal product code |
LY2835219
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
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.
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Baseline characteristics reporting groups
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Reporting group title |
200 Milligram (mg) Abemaciclib Twice Daily
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Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
200 Milligram (mg) Abemaciclib Twice Daily
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Reporting group 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. | ||
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End point title |
Percentage of Participants With Confirmed Objective Response (Objective Response Rate [ORR]) [1] | ||||||||
End point 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. Analysis population description (APD): All participants who received at least one dose of the study drug.
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End point type |
Primary
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End point timeframe |
From Date of First Dose until Objective Progression (Up To 12.8 Months)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential statistics was planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Radiographic Progression-Free Survival (rPFS) | ||||||||
End point 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. APD: All participants who received at least one dose of the study drug. Participants censored = 11.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Objective Progression or Death from Any Cause (Up To 12.8 Months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR]) | ||||||||
End point 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. APD: All participants who received at least one dose of the study drug.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Measured Progressive Disease or Death Due to Any Cause (Up To 12.8 Months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Prostate-Specific Antigen (PSA) Progression | ||||||||
End point 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 percent (%) 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. APD: All participants who received at least one dose of the study drug. Participants censored: 31. The upper 95% confidence interval (CI) not achieved as there were insufficient number of events due to high censoring rate.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months)
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| Notes [2] - 9999=Data not available. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response (PSA Response Rate) | ||||||||
End point 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. APD: All participants who received at least one dose of the study drug.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Symptomatic Progression | ||||||||
End point 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. APD: All participants who received at least one dose of the study drug. Participants censored = 28.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Symptomatic Progression (Up to 12.8 Months)
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| Notes [3] - 9999=Data not available; Upper 95% confidence interval (CI) not achieved due to high censoring rate. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Pharmacokinetics (PK): Maximum Plasma Concentration at steady state (Cmax,ss) of Abemaciclib | ||||||||
End point description |
PK: Cmax,ss of abemaciclib is reported. The cycle length was 28 days. APD: All participants who received at least one dose of study drug had evaluable PK data.
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End point type |
Secondary
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End point timeframe |
Cycle (C) 1 Day (D) 1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose
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| No statistical analyses for this end point | |||||||||
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End point title |
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib | ||||||||
End point description |
PK: Cmin,ss of abemaciclib is reported. APD: All participants who received at least one dose of study drug had evaluable PK data.
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End point type |
Secondary
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End point timeframe |
C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose
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| No statistical analyses for this end point | |||||||||
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End point title |
PK: Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib Metabolites (Total Active Species) | ||||||||
End point description |
PK: Cmax,ss of abemaciclib metabolites (Total Active Species) is reported. APD: All participants who received at least one dose of study drug had evaluable PK data.
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End point type |
Secondary
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End point timeframe |
C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose
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| No statistical analyses for this end point | |||||||||
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End point title |
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib Metabolites (Total Active Species) | ||||||||
End point description |
PK: Cmin,ss of abemaciclib metabolites (Total Active Species) is reported. APD: All participants who received at least one dose of study drug had evaluable PK data.
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End point type |
Secondary
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End point timeframe |
C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Expression of Ki-67 proliferation marker by Immunohistochemistry (IHC) | ||||||||||||
End point 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 proportion 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. APD: All participants with evaluable tumor tissue specimens
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End point type |
Secondary
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End point timeframe |
Baseline
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point 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. APD:All participants who received at least one dose of the study drug. Participants censored = 13.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Date of Death from Any Cause (Up To 28 Months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DoR) | ||||||||
End point 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. APD: All randomized participants who received at least one dose of the study drug and had CR or PR responses. The median was not achieved due to insufficient sample data.
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End point type |
Secondary
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End point timeframe |
CR or PR to Disease Progression or Death Due to Any Cause (Up to 12 Months)
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| Notes [4] - 9999=Data not available for median due to insufficient sample data. Full range values=3.87 to 11.17. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline Up to 28 Months
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Adverse event reporting additional description |
All participants who received at least one dose of the study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
200 mg Abemaciclib Twice Daily
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Reporting group description |
Participants received 200 mg of 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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24 Sep 2020 |
- Clarification of Primary Endpoint; - Added mobile healthcare service option to collect and process lab, PK, Plasma/blood samples; -Added blood microsampling to PK sampling schedule; -Updated new treatment options for metastatic castration-resistant prostate cancer (mCRPC) where approved; - Clarification of Inclusion and Exclusion Criterion; - Text was added to caution participants with known hypersensitivity or suspected intolerance to abemaciclib or any of its excipients; - Clarifications: For Study Intervention(s) Administered; Preparation/Handling/Storage/Accountability regarding study drug; Selection and Timing of Doses; Concomitant Therapy; Discontinuation of Inadvertently Enrolled Participants; Lost to Follow up; Definitions of Efficacy Measures; Clinical Safety Laboratory Assessments; PK; Health Care Resource Utilization; Regulatory and Ethical Considerations; - Updated instructions for Data Quality Assurance |
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04 Mar 2021 |
- Added clarification to Schedule of Activities, Lifestyle Considerations, Selection and Timing of Doses; - Updated language for CYP3A modulators and transporter substrates; - Formatted table for toxicity dose adjustments and delays of abemaciclib; - Updated guidance for monitoring renal function, guidance for venous thromboembolic events, guidance for interstitial lung disease/pneumonitis; - Editorial changes to clarify study statistics; - Added alanine transaminase (ALT) and aspartate transaminase (AST) to the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 table and updated Appendix title and summary text to reflect these additions. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
