Breast Neoplasms
Conditions
Brief summary
The main purpose of this study is to measure how well abemaciclib works in participants with early breast cancer who are taking hormone therapy after surgery. Participants must have breast cancer that is hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+). Your participation could last up to 10 years depending on how you and your tumor respond.
Interventions
DRUGAbemaciclib
Administered orally.
DRUGStandard Adjuvant ET
Administered according to label instructions.
DRUGPlacebo
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have confirmed HR+, HER2+ early invasive breast cancer without evidence of disease recurrence or distant metastases * Have undergone definitive surgery of the primary breast tumor(s) * Have tumor tissue from breast (preferred) or lymph node * Have received a minimum of four cycles of chemotherapy in either the neoadjuvant or adjuvant setting per standard of care * Have completed approximately nine to 20 months of standard HER2-targeted therapy (neoadjuvant/adjuvant combined duration) * Have received one of the following eligible HER2-targeted adjuvant regimens AND be randomized within 12 weeks of completing the regimen: * For participants treated with neoadjuvant therapy and HER2-targeted therapy: A minimum of 4 cycles of T-DM1 in the adjuvant setting. NOTE: Participants may have received up to approximately 6 cycles of adjuvant trastuzumab prior to initiation of T-DM1. Additionally, participants may have switched to trastuzumab-based therapy (monotherapy or in combination with other HER2-targeted therapies) after 4 cycles of T-DM1 * For participants who had definitive surgery prior to systemic therapy, a minimum of 4 cycles of adjuvant pertuzumab with trastuzumab. * Have high risk disease, defined by one of the following criteria: * Those who received neoadjuvant chemotherapy along with HER2-targeted treatment must have: * residual disease in at least one axillary lymph node, or * a residual tumor ≥ 5 cm, or * a residual tumor of any size that has direct extension to the chest wall and/or skin (ulceration or skin nodules). * Those who had definitive surgery prior to systemic therapy and completed adjuvant chemotherapy along with HER2-targeted therapies (trastuzumab and pertuzumab) must have * tumor involvement in ≥4 ipsilateral axillary lymph nodes, or * tumor involvement in 1 to 3 ipsilateral axillary lymph node(s) and histological Grade 3, or * primary invasive tumor size of ≥ 5 cm on pathological evaluation.
Exclusion criteria
* Have breast cancer with any of the following features: * Disease recurrence or distant metastatic disease (including contralateral axillary lymph nodes) * Pathological complete response from any prior early breast cancer treatments. Participants are required to have residual primary tumor and/or lymph node disease at the time of definitive surgery as indicated in inclusion criteria. * Inflammatory breast cancer * Have other medical conditions including: * Previous breast cancer (Exceptions: Ipsilateral ductal carcinoma in situ \[DCIS\] treated by locoregional therapy alone ≥5 years ago; contralateral DCIS treated by locoregional therapy at any time) * Other cancer being treated and/or not in complete remission within the last 5 years (Exceptions: Appropriately treated non-melanomatous skin cancer or carcinoma in situ of cervix, bladder, or colon) * Females who are pregnant or lactating * History of venous thromboembolism * Other serious medical conditions * Have previously received treatment with: * Any cyclin-dependent kinase (CDK)4 and CDK6 inhibitor * Prior adjuvant treatment with immunotherapy, tucatinib, neratinib, any investigational HER2 directed therapy, or T-DXd (DS8201) for treatment of breast cancer * Endocrine therapy (ET) (i.e., tamoxifen, raloxifene or aromatase inhibitor) for breast cancer prevention (without diagnosis of breast cancer) * Additional chemotherapy, anti-cancer ET, or HER2-targeted therapy beyond standard of care at study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease Free Survival (IDFS) | Randomization to Recurrence or Death from Any Cause (up to 890 days) | IDFS, as defined by the STEEP System, is measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant Relapse-Free Survival (DRFS) | Randomization to Distant Recurrence or Death from Any Cause (up to 890 days) | DRFS is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed. |
| Percentage of Participants With Central Nervous System (CNS) Metastases as First Site of Disease Recurrence | Randomization to Distant Recurrence or Death from Any Cause (up to 890 days) | Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed. |
| Overall Survival (OS) | Randomization to Death from Any Cause (up to 890 days) | OS is defined as the time from randomization until death from any cause. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed. |
| Change From Baseline in the EuroQOL 5 Dimension 5 Level (EQ-5D 5L) Index Score | Cycle 1 up to 390 days | 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 are anchored on a scale of 0 to 1 with a higher score representing better health status. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed. |
| Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib | Day 1 of Cycles 1-3 (Cycle = 28 days) | Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed. |
| Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale Score | Cycle 1 up to 390 days | The EORTC QLQ-C30 (v. 3.0) is a self-administered, cancer-specific questionnaire with multidimensional scales assessing 15 domains (5 functional domains, 9 symptoms, and global health status). A linear transformation will be applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptom scales, higher scores represent a greater degree of symptoms. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, China, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was terminated early due to inability to enroll study participants. Data was not collected after termination and outcome measures were not assessed.
Pre-assignment details
Completers were defined as participants who received abemaciclib and were allowed to stay on treatment in the study. Participants receiving placebo discontinued after the study was terminated.
Participants by arm
| Arm | Count |
|---|---|
| 150 mg Abemaciclib + ET Participants received 150 mg of abemaciclib administered BID orally along with standard adjuvant ET. | 55 |
| Placebo + ET Participants received placebo administered BID orally along with standard adjuvant ET. | 56 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Disease Relapse | 1 | 0 |
| Overall Study | Non-compliance With Study Drug | 2 | 0 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Study Terminated by IRB/ERB | 0 | 2 |
| Overall Study | Study Terminated by Sponsor | 10 | 48 |
| Overall Study | Withdrawal by Subject | 11 | 3 |
Baseline characteristics
| Characteristic | Total | 150 mg Abemaciclib + ET | Placebo + ET |
|---|---|---|---|
| Age, Continuous | 49.20 years STANDARD_DEVIATION 11.43 | 48.60 years STANDARD_DEVIATION 11.76 | 49.70 years STANDARD_DEVIATION 11.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 9 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 85 Participants | 44 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 49 Participants | 26 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 56 Participants | 27 Participants | 29 Participants |
| Region of Enrollment Argentina | 9 participants | 4 participants | 5 participants |
| Region of Enrollment Australia | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Austria | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Belgium | 4 participants | 2 participants | 2 participants |
| Region of Enrollment Brazil | 6 participants | 3 participants | 3 participants |
| Region of Enrollment China | 27 participants | 12 participants | 15 participants |
| Region of Enrollment France | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Germany | 3 participants | 2 participants | 1 participants |
| Region of Enrollment Greece | 8 participants | 4 participants | 4 participants |
| Region of Enrollment Hungary | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Israel | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Italy | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Japan | 10 participants | 7 participants | 3 participants |
| Region of Enrollment Mexico | 2 participants | 1 participants | 1 participants |
| Region of Enrollment South Korea | 6 participants | 4 participants | 2 participants |
| Region of Enrollment Spain | 8 participants | 3 participants | 5 participants |
| Region of Enrollment Switzerland | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Taiwan | 4 participants | 1 participants | 3 participants |
| Region of Enrollment United Kingdom | 5 participants | 1 participants | 4 participants |
| Region of Enrollment United States | 8 participants | 5 participants | 3 participants |
| Sex: Female, Male Female | 110 Participants | 54 Participants | 56 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 56 |
| other Total, other adverse events | 53 / 55 | 40 / 56 |
| serious Total, serious adverse events | 6 / 55 | 2 / 56 |
Outcome results
Primary
Invasive Disease Free Survival (IDFS)
IDFS, as defined by the STEEP System, is measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Time frame: Randomization to Recurrence or Death from Any Cause (up to 890 days)
Population: Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Secondary
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale Score
The EORTC QLQ-C30 (v. 3.0) is a self-administered, cancer-specific questionnaire with multidimensional scales assessing 15 domains (5 functional domains, 9 symptoms, and global health status). A linear transformation will be applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptom scales, higher scores represent a greater degree of symptoms. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Time frame: Cycle 1 up to 390 days
Population: Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Secondary
Change From Baseline in the EuroQOL 5 Dimension 5 Level (EQ-5D 5L) Index Score
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 are anchored on a scale of 0 to 1 with a higher score representing better health status. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Time frame: Cycle 1 up to 390 days
Population: Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Secondary
Distant Relapse-Free Survival (DRFS)
DRFS is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Time frame: Randomization to Distant Recurrence or Death from Any Cause (up to 890 days)
Population: Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Secondary
Overall Survival (OS)
OS is defined as the time from randomization until death from any cause. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Time frame: Randomization to Death from Any Cause (up to 890 days)
Population: Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Secondary
Percentage of Participants With Central Nervous System (CNS) Metastases as First Site of Disease Recurrence
Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Time frame: Randomization to Distant Recurrence or Death from Any Cause (up to 890 days)
Population: Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Secondary
Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib
Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
Time frame: Day 1 of Cycles 1-3 (Cycle = 28 days)
Population: Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.