Clinical Trial Results:
A Phase 2 Study of LY2835219 for Patients with Previously Treated Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer
Summary
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EudraCT number |
2013-005548-27 |
Trial protocol |
BE ES |
Global end of trial date |
22 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Sep 2019
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First version publication date |
01 Sep 2019
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Other versions |
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-JPBN
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02102490 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Trial Number: 15419 | ||
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 |
22 Oct 2018
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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 |
22 Oct 2018
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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 main purpose of this study is to evaluate whether the study drug known as abemaciclib is effective in treating participants with breast cancer who have already tried other drug 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 |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Jun 2014
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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 |
Belgium: 28
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Country: Number of subjects enrolled |
United States: 70
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Country: Number of subjects enrolled |
France: 11
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Country: Number of subjects enrolled |
Spain: 23
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Worldwide total number of subjects |
132
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EEA total number of subjects |
62
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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) |
90
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From 65 to 84 years |
41
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||||||||||
Pre-assignment
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Screening details |
In the Participant Flow, participants who completed were those who died due to any cause or were alive and on study at conclusion but off treatment. | ||||||||||||||
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 | ||||||||||||||
Arms
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Arm title
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Abemaciclib | ||||||||||||||
Arm description |
200 mg abemaciclib given orally once every 12 hours for 28 days (1 cycle). Participants may continue to receive treatment until discontinuation criteria are met. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Abemaciclib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
200 mg abemaciclib given orally once every 12 hours for 28 days (1 cycle).
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
200 mg abemaciclib given orally once every 12 hours for 28 days (1 cycle). Participants may continue to receive treatment until discontinuation criteria are met. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Abemaciclib
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Reporting group description |
200 mg abemaciclib given orally once every 12 hours for 28 days (1 cycle). Participants may continue to receive treatment until discontinuation criteria are met. |
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End point title |
Percentage of Participants with Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) [1] | ||||||||
End point description |
ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Analysis
population included all enrolled participants who received at least one dose of study drug.
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End point type |
Primary
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End point timeframe |
From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 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 were planned or conducted for this endpoint. |
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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 defined as the time from first dose date to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. 9999=Data Not Available (N/A) as upper limit of the 95% confidence interval (CI) was not calculated due to the high censoring rate. Analysis
population included all enrolled participants who received at least one dose of study drug. Censored participants: Abemaciclib=70.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Death Due to Any Cause (Up To 27 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 was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. Analysis population included all enrolled participants who received at least one dose of study drug.
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End point type |
Secondary
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End point timeframe |
From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 14 Months)
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No statistical analyses for this end point |
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End point title |
Progression Free Survival (PFS) | ||||||||
End point description |
PFS defined as the time from the first day of therapy to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at last adequate tumor assessment date. Analysis population included all enrolled participants who received at least one dose of study drug. Censored participants: Abemaciclib=35.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 27 Months)
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with CR, PR or SD (Disease Control Rate [DCR]) | ||||||||
End point description |
Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Analysis population included all enrolled participants who received at least one dose of study drug.
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End point type |
Secondary
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End point timeframe |
From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months)
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Tumor Response of Stable Disease (SD) for at least 6 months, Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) | ||||||||
End point description |
Clinical benefit rate defined as percentage of patients with best overall response of CR, PR, or SD with a duration of at least 6 months. CR, PR, or SD were defined using RECIST, v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Percentage of participants = (participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) *100. Analysis population included all enrolled 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 Disease Progression or Death Due to Any Cause (Up To 14 Months)
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No statistical analyses for this end point |
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End point title |
Number of Participants with Categorical Change From Baseline in Brief Pain Inventory Short Form (mBPI-sf) - Worst Pain Score | ||||||
End point description |
A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Analysis population included all randomized participants with a baseline and at least 1 post-baseline mBPI-sf data.
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End point type |
Secondary
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End point timeframe |
Cycle 6 Day 1
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No statistical analyses for this end point |
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End point title |
Pharmacokinetics: Area Under the Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) for Abemaciclib and Metabolites M2 and M20 | ||||||||||||||
End point description |
Area Under the Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) was evaluated for Abemaciclib and Metabolites M2 and M20. Analysis population included all enrolled participants who received at least one dose of study drug (Abemaciclib) with evaluable Abemaciclib, M2 and M20 pharmacokinetic (PK) data.
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End point type |
Secondary
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End point timeframe |
Cycle 1 Day 1 pre dose, Cycle 1 Day 15 4 hours (h) and 7 h post dose, Cycle 2 Day 1 pre dose and 3 h post dose, Cycle 3 Day1 pre dose
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No statistical analyses for this end point |
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End point title |
Number of Participants with Categorical Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status Score | ||||||||||||
End point description |
EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. Analysis population included all randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-C30 data.
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End point type |
Secondary
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End point timeframe |
Cycle 6 Day 1
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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 |
Up To 45.57 Months
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Adverse event reporting additional description |
All enrolled participants who received at least one dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
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Reporting groups
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Reporting group title |
Abemaciclib
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Reporting group description |
200 mg abemaciclib given orally once every 12 hours for 28 days (1 cycle). Participants may continue to receive treatment until discontinuation criteria are 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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26 Mar 2015 |
- Amended to change the time of primary efficacy analysis of ORR from 8 months to 12 months after last patient has entered treatment and to consider the efficacy analysis of ORR at 8 months as an interim efficacy analysis. The time of primary efficacy analysis was changed to ensure adequate response and that durability of response data is available for analysis. The interim efficacy analysis at 8 months allows an earlier assessment of efficacy. In addition, the primary efficacy measure was modified to use investigator-assessed tumor response, which would allow for evaluation earlier than independently reviewed tumor response.
- Further modifications were made for 1) supportive management of diarrhea, 2) health outcomes, and 3) Study Schedule for clarity.
- Minor typographical and formatting edits were made throughout the document for clarity and consistency. |
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16 Oct 2015 |
- Updated the dosing guidance for cases of hematologic toxicity and diarrhea, and guidance on the use of blood cell growth factors. Lilly conducted a review across several clinical trials of abemaciclib in breast cancer and concluded that there were some inconsistencies. This amendment harmonized the dosing guidance and clarified that blood cell growth factors are only to be used in a manner consistent with American Society of Clinical Oncology (ASCO) guidelines.
-Minor typographical and formatting edits were made throughout the document for clarity and consistency.
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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 |