Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02675231




Registration number
NCT02675231
Ethics application status
Date submitted
3/02/2016
Date registered
5/02/2016
Date last updated
26/11/2024

Titles & IDs
Public title
A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer
Scientific title
monarcHER: A Phase 2, Randomized, Multicenter, 3-Arm, Open-Label Study to Compare the Efficacy of Abemaciclib Plus Trastuzumab With or Without Fulvestrant to Standard-of-Care Chemotherapy of Physician's Choice Plus Trastuzumab in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer
Secondary ID [1] 0 0
I3Y-MC-JPBZ
Secondary ID [2] 0 0
15804
Universal Trial Number (UTN)
Trial acronym
monarcHER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hormone Receptor Positive Breast Cancer 0 0
HER-2 Positive Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Abemaciclib
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Standard of Care Single Agent Chemotherapy

Experimental: 150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant - 150 milligram (mg) abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 milligram per kilogram (mg/kg) trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500 mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.

Experimental: 150 mg Abemaciclib + 8 mg/kg Trastuzumab - 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.

Active comparator: 8 mg/kg Trastuzumab + Standard of Care Chemotherapy - 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label


Treatment: Drugs: Abemaciclib
Administered Orally

Treatment: Drugs: Trastuzumab
Administered IV

Treatment: Drugs: Fulvestrant
Administered IM

Treatment: Drugs: Standard of Care Single Agent Chemotherapy
Standard-of-care single-agent chemotherapy of physician's choice administered according to product label
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Assessment method [1] 0 0
PFS time was measured from the date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, 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 the last adequate tumor assessment date.
Timepoint [1] 0 0
Baseline to Progressive Disease or Death from Any Cause (Up To 36 Months)
Secondary outcome [1] 0 0
Percentage of Participants With 1 Year Overall Survival (OS)
Assessment method [1] 0 0
OS is defined as the time from the date of randomization until death from any cause. For participants not known to have died by the data-inclusion cutoff date, OS is censored at the last date they were known to be alive. For each treatment arm OS rate at 1 year from the date of randomization was determined using the OS times and was estimated using the Kaplan-Meier method.
Timepoint [1] 0 0
Randomization to date of death from any cause assessed at 1 year
Secondary outcome [2] 0 0
Percentage of Participants With 2 Year OS
Assessment method [2] 0 0
OS is defined as the time from the date of randomization until death from any cause. For participants not known to have died by the data-inclusion cutoff date, OS is censored at the last date they were known to be alive. For each treatment arm OS rate at 2 years from the date of randomization was determined using the OS times and was estimated using the Kaplan-Meier method.
Timepoint [2] 0 0
Randomization to date of death from any cause assessed at 2 years
Secondary outcome [3] 0 0
Percentage of Participants With 3 Year OS
Assessment method [3] 0 0
OS is defined as the time from the date of randomization until death from any cause. For participants not known to have died by the data-inclusion cutoff date, OS is censored at the last date they were known to be alive. For each treatment arm OS rate at 3 years from the date of randomization was determined using the OS times and was estimated using the Kaplan-Meier method.
Timepoint [3] 0 0
Randomization to date of death from any cause assessed at 3 years
Secondary outcome [4] 0 0
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline to Objective Disease Progression (Up To 36 Months)
Secondary outcome [5] 0 0
Duration of Response (DoR)
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up To 36 Months)
Secondary outcome [6] 0 0
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Baseline to Objective Disease Progression (Up To 36 Months)
Secondary outcome [7] 0 0
Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months: Clinical Benefit Rate (CBR)
Assessment method [7] 0 0
Clinical benefit rate defined as percentage of participants 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.
Timepoint [7] 0 0
Date of CR, PR or SD to 6 Months Post CR, PR or SD (Up To 36 Months)
Secondary outcome [8] 0 0
Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)
Assessment method [8] 0 0
The mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours and typical completion time for this instrument is less than 5 minutes. Mean Interference Score data is reported here. Least square (LS) Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.
Timepoint [8] 0 0
Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)
Secondary outcome [9] 0 0
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
Assessment method [9] 0 0
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. LS Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.
Timepoint [9] 0 0
Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)
Secondary outcome [10] 0 0
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
Assessment method [10] 0 0
The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Participants completed the 5-level (no problem, slight problem, moderate problem, severe problem, and inability or extreme problem), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. Five dimensions of health status are each assessed with 5 response options and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status.LS Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.
Timepoint [10] 0 0
Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)
Secondary outcome [11] 0 0
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)
Assessment method [11] 0 0
European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.
Timepoint [11] 0 0
Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)
Secondary outcome [12] 0 0
Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20)
Assessment method [12] 0 0
Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20) was evaluated. M2 and M20 are 2 major active metabolites of abemaciclib.
Timepoint [12] 0 0
Cycle(C)1 Day(D)1,C1D15, C2D1, C2D8, C3D1,C3D15, C4D1, C5D1:pre-dose; C1D1, C2D1, C3D1, C4D1, C5D1:post-dose

Eligibility
Key inclusion criteria
* diagnosis of HR+, HER2+ breast cancer (BC)
* unresectable locally advanced recurrent BC or metastatic BC
* adequate tumor tissue available prior to randomization
* measurable and/or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* previously received:

* at least 2 HER2-directed therapies for advanced disease
* participant must have received trastuzumab emtansine (T-DM1) in any disease setting
* must have received a taxane in any disease setting
* may have received any endocrine therapy (excluding fulvestrant)
* have postmenopausal status due to surgical / natural menopause or chemical ovarian suppression
* performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale
* left ventricular ejection fraction (LVEF) of 50% or higher at baseline
* adequate organ function
* negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if menopause induced by gonadotropin-releasing hormone (GnRH) agonist or radiation
* discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture at least 2 weeks prior to randomization and recovered from the acute effects of therapy
* discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and endocrine therapy), except trastuzumab, for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy
* are able to swallow capsules
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* have visceral crisis
* known central nervous system (CNS) metastases that are untreated, symptomatic, or require steroids to control symptoms
* had major surgery within 14 days prior to randomization
* received prior treatment with any cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor
* received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively
* have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study
* history within the last 6 months of symptomatic congestive heart failure, myocardial infarction, or unstable angina
* history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
* history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
* active bacterial, fungal infection, or detectable viral infection
* have received any recent (within 28 days prior to randomization) live virus vaccination
* hypersensitivity to trastuzumab, murine proteins, fulvestrant, or to any of the excipients

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/05/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/11/2023
Sample size
Target
Accrual to date
Final
237
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Kurralta Park
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Nedlands
Recruitment hospital [3] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - St. Leonards
Recruitment postcode(s) [1] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
2065 - St. Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Montana
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Caba
Country [17] 0 0
Argentina
State/province [17] 0 0
Cordoba
Country [18] 0 0
Argentina
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La Rioja
Country [19] 0 0
Argentina
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Rosario
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Argentina
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San Miguel De Tucuman
Country [21] 0 0
Argentina
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Viedma
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Belgium
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Charleroi
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Namur
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Brazil
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Porto Alegre
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Brazil
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Rio de Janeiro
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Brazil
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Sao Paulo
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Brazil
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São Paulo
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Canada
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Calgary
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Canada
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Newmarket
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Canada
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Ottawa
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France
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Angers
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France
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Besancon
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France
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Lyon
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France
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Montpellier
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France
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Nice
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France
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Paris
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France
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Saint Cloud
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France
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Villejuif
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Germany
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Frankfurt am Main
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Germany
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Freiburg
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Germany
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Hamburg
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Germany
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München
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Greece
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Achaia
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Greece
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Athens
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Italy
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Genova
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Italy
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Milano
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Italy
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Sora
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Korea, Republic of
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Daegu
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
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Seoul
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Mexico
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Mexico City
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Mexico
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Mexico
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Mexico
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México City
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Spain
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Badajoz
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Sevilla
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United Kingdom
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Leicester
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United Kingdom
State/province [62] 0 0
Manchester
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United Kingdom
State/province [63] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02675231