Metastatic Breast Cancer
Conditions
Brief summary
The main purpose of this study is to examine the side effects that participants with metastatic breast cancer experience when taking abemaciclib with or without food.
Interventions
DRUGAbemaciclib
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of HR+, HER2- metastatic breast cancer (mBC). * Have all of the following: * Recurrent, locally advanced, unresectable or mBC with disease progression following anti-estrogen therapy. * Prior treatment with chemotherapy for locally advanced or metastatic disease. * No prior treatment with cyclin-dependent kinases (CDK) 4 and 6 inhibitor. * Have Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1. * Have discontinued all previous treatments for cancer and recovered from the acute effects of therapy. * Have adequate organ function. * Women of child-bearing potential must have a negative pregnancy test. * Are able to swallow tablets/capsules.
Exclusion criteria
* Are currently receiving treatment in a clinical study involving an investigational product. * Have a serious concomitant systemic disorder. * Have symptomatic central nervous system (CNS) malignancy or metastasis. * Have a symptomatic Human Immunodeficiency Virus (HIV) infection or symptomatic activated/reactivated hepatitis A, B, or C. * Have a personal history of syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest. * Have a history of any other cancer. * Had major surgery within 14 days prior to randomization. * Are breastfeeding. * Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Utilizing Antidiarrheals | Cycle 3 (28 Days Cycle) | Percentage of participants who utilized anti diarrheals at least once during the first 3 cycles. |
| Percentage of Participants With Dose Reductions Due to Diarrhea | Cycle 3 (28 Days Cycle) | Percentage of participants with dose reductions due to diarrhea during first 3 cycles. |
| Percentage of Participants With Dose Interruptions Due to Diarrhea | Cycle 3 (28 Days Cycle) | Percentage of participants with dose interruptions due to diarrhea during first 3 cycles. |
| Percentage of Participants Who Discontinue Treatment Due to Diarrhea | Cycle 3 (28 Days Cycle) | Percentage of participants who discontinue treatment due to diarrhea |
| Percentage of Participants With Severe Diarrhea (≥ Grade 3) | Cycle 3 (28 Days Cycle) | Percentage of participants with severe diarrhea (≥ grade 3) during the first 3 cycles. Events were as assessed by the investigator and graded according to Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 was defined as an increase of ≥7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care activities of daily living (ADL). |
| Percentage of Participants With Prolonged Grade 2 Diarrhea | Cycle 3 (28 Days Cycle) | Percentage of participants with prolonged grade 2 diarrhea during first 3 cycles. Events were as assessed by the investigator and graded according to Common Terminology Criteria for Adverse Events (CTCAE). Prolonged Grade 2 diarrhea was any event lasting more than 7 days. Grade 2 was defined as Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 1: Day 15; Cycle 2: Day1, Day 15; Cycle 3: Day 1 (28 Days Cycle) | PK: Mean steady state exposure of abemaciclib metabolite LSN2839567 |
| PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 1: Day 15; Cycle 2: Day1, Day 15; Cycle 3: Day 1 (28 Days Cycle) | PK: Mean steady state exposure of abemaciclib metabolite LSN3106726 |
| Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 1: Day 15; Cycle 2: Day 1, Day 15; Cycle 3: Day 1 (28 Days Cycle) | PK: Mean steady state exposure of abemaciclib |
Countries
Australia, Belgium, Russia, Spain, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 200 mg Abemaciclib With a Meal 200 mg abemaciclib given twice a day (BID) orally with a meal. | 24 |
| 200 mg Abemaciclib Without a Meal 200 mg abemaciclib given twice a day (BID) orally without a meal, taken in the modified fasted condition. | 24 |
| 200 mg Abemaciclib Without Regard to Food 200 mg abemaciclib given twice a day (BID) orally without regard for food. | 24 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Completed < 3 Cycles | 2 | 2 | 2 |
| Overall Study | Death | 2 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | 200 mg Abemaciclib With a Meal | 200 mg Abemaciclib Without a Meal | 200 mg Abemaciclib Without Regard to Food | Total |
|---|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 11.6 | 56.9 years STANDARD_DEVIATION 11.1 | 57.6 years STANDARD_DEVIATION 8.3 | 57.6 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 19 Participants | 20 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 24 Participants | 24 Participants | 70 Participants |
| Region of Enrollment Australia | 11 Participants | 10 Participants | 10 Participants | 31 Participants |
| Region of Enrollment Belgium | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Russia | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Spain | 6 Participants | 6 Participants | 7 Participants | 19 Participants |
| Region of Enrollment Turkey | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Female | 23 Participants | 24 Participants | 24 Participants | 71 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 24 | 4 / 23 | 1 / 24 |
| other Total, other adverse events | 24 / 24 | 23 / 23 | 24 / 24 |
| serious Total, serious adverse events | 3 / 24 | 5 / 23 | 8 / 24 |
Outcome results
Primary
Percentage of Participants Utilizing Antidiarrheals
Percentage of participants who utilized anti diarrheals at least once during the first 3 cycles.
Time frame: Cycle 3 (28 Days Cycle)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 mg Abemaciclib With a Meal | Percentage of Participants Utilizing Antidiarrheals | 95.8 percentage of participants |
| 200 mg Abemaciclib Without a Meal | Percentage of Participants Utilizing Antidiarrheals | 91.3 percentage of participants |
| 200 mg Abemaciclib Without Regard to Food | Percentage of Participants Utilizing Antidiarrheals | 95.8 percentage of participants |
Primary
Percentage of Participants Who Discontinue Treatment Due to Diarrhea
Percentage of participants who discontinue treatment due to diarrhea
Time frame: Cycle 3 (28 Days Cycle)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 mg Abemaciclib With a Meal | Percentage of Participants Who Discontinue Treatment Due to Diarrhea | 0 percentage of participants |
| 200 mg Abemaciclib Without a Meal | Percentage of Participants Who Discontinue Treatment Due to Diarrhea | 0 percentage of participants |
| 200 mg Abemaciclib Without Regard to Food | Percentage of Participants Who Discontinue Treatment Due to Diarrhea | 0 percentage of participants |
Primary
Percentage of Participants With Dose Interruptions Due to Diarrhea
Percentage of participants with dose interruptions due to diarrhea during first 3 cycles.
Time frame: Cycle 3 (28 Days Cycle)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 mg Abemaciclib With a Meal | Percentage of Participants With Dose Interruptions Due to Diarrhea | 16.7 percentage of participants |
| 200 mg Abemaciclib Without a Meal | Percentage of Participants With Dose Interruptions Due to Diarrhea | 4.3 percentage of participants |
| 200 mg Abemaciclib Without Regard to Food | Percentage of Participants With Dose Interruptions Due to Diarrhea | 8.3 percentage of participants |
Primary
Percentage of Participants With Dose Reductions Due to Diarrhea
Percentage of participants with dose reductions due to diarrhea during first 3 cycles.
Time frame: Cycle 3 (28 Days Cycle)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 mg Abemaciclib With a Meal | Percentage of Participants With Dose Reductions Due to Diarrhea | 16.7 percentage of participants |
| 200 mg Abemaciclib Without a Meal | Percentage of Participants With Dose Reductions Due to Diarrhea | 8.7 percentage of participants |
| 200 mg Abemaciclib Without Regard to Food | Percentage of Participants With Dose Reductions Due to Diarrhea | 12.5 percentage of participants |
Primary
Percentage of Participants With Prolonged Grade 2 Diarrhea
Percentage of participants with prolonged grade 2 diarrhea during first 3 cycles. Events were as assessed by the investigator and graded according to Common Terminology Criteria for Adverse Events (CTCAE). Prolonged Grade 2 diarrhea was any event lasting more than 7 days. Grade 2 was defined as Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline.
Time frame: Cycle 3 (28 Days Cycle)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 mg Abemaciclib With a Meal | Percentage of Participants With Prolonged Grade 2 Diarrhea | 8.3 percentage of participants |
| 200 mg Abemaciclib Without a Meal | Percentage of Participants With Prolonged Grade 2 Diarrhea | 17.4 percentage of participants |
| 200 mg Abemaciclib Without Regard to Food | Percentage of Participants With Prolonged Grade 2 Diarrhea | 20.8 percentage of participants |
Primary
Percentage of Participants With Severe Diarrhea (≥ Grade 3)
Percentage of participants with severe diarrhea (≥ grade 3) during the first 3 cycles. Events were as assessed by the investigator and graded according to Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 was defined as an increase of ≥7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care activities of daily living (ADL).
Time frame: Cycle 3 (28 Days Cycle)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 200 mg Abemaciclib With a Meal | Percentage of Participants With Severe Diarrhea (≥ Grade 3) | 4.2 percentage of participants |
| 200 mg Abemaciclib Without a Meal | Percentage of Participants With Severe Diarrhea (≥ Grade 3) | 0 percentage of participants |
| 200 mg Abemaciclib Without Regard to Food | Percentage of Participants With Severe Diarrhea (≥ Grade 3) | 0 percentage of participants |
Secondary
Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib
PK: Mean steady state exposure of abemaciclib
Time frame: Cycle 1: Day 15; Cycle 2: Day 1, Day 15; Cycle 3: Day 1 (28 Days Cycle)
Population: All participants who received at least one dose of study drug who had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 200 mg Abemaciclib With a Meal | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 1: Day 15 | 305 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 198 |
| 200 mg Abemaciclib With a Meal | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 2: Day 1 | 320 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 91 |
| 200 mg Abemaciclib With a Meal | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 2: Day 15 | 77.4 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 731 |
| 200 mg Abemaciclib With a Meal | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 3: Day 1 | 135 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 896 |
| 200 mg Abemaciclib Without a Meal | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 3: Day 1 | 330 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 54 |
| 200 mg Abemaciclib Without a Meal | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 1: Day 15 | 369 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 64 |
| 200 mg Abemaciclib Without a Meal | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 2: Day 15 | 345 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| 200 mg Abemaciclib Without a Meal | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 2: Day 1 | 280 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 99 |
| 200 mg Abemaciclib Without Regard to Food | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 3: Day 1 | 85.4 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 498 |
| 200 mg Abemaciclib Without Regard to Food | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 2: Day 1 | 190 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 284 |
| 200 mg Abemaciclib Without Regard to Food | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 2: Day 15 | 223 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 250 |
| 200 mg Abemaciclib Without Regard to Food | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | Cycle 1: Day 15 | 356 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 75 |
Secondary
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567
PK: Mean steady state exposure of abemaciclib metabolite LSN2839567
Time frame: Cycle 1: Day 15; Cycle 2: Day1, Day 15; Cycle 3: Day 1 (28 Days Cycle)
Population: All participants who received at least one dose of study drug who had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 200 mg Abemaciclib With a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 2 Day 1 | 125 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 62 |
| 200 mg Abemaciclib With a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 2 Day 15 | 50.4 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 276 |
| 200 mg Abemaciclib With a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 1 Day 15 | 139 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 109 |
| 200 mg Abemaciclib With a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 3 Day 1 | 89.4 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 110 |
| 200 mg Abemaciclib Without a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 2 Day 1 | 109 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 84 |
| 200 mg Abemaciclib Without a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 1 Day 15 | 129 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| 200 mg Abemaciclib Without a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 2 Day 15 | 121 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 45 |
| 200 mg Abemaciclib Without a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 3 Day 1 | 125 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| 200 mg Abemaciclib Without Regard to Food | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 2 Day 15 | 112 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 79 |
| 200 mg Abemaciclib Without Regard to Food | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 1 Day 15 | 159 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 61 |
| 200 mg Abemaciclib Without Regard to Food | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 2 Day 1 | 96.3 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 127 |
| 200 mg Abemaciclib Without Regard to Food | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 | Cycle 3 Day 1 | 61.7 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 122 |
Secondary
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726
PK: Mean steady state exposure of abemaciclib metabolite LSN3106726
Time frame: Cycle 1: Day 15; Cycle 2: Day1, Day 15; Cycle 3: Day 1 (28 Days Cycle)
Population: All participants who received at least one dose of study drug who had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 200 mg Abemaciclib With a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 1 Day 15 | 231 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 120 |
| 200 mg Abemaciclib With a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 2 Day 1 | 230 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 59 |
| 200 mg Abemaciclib With a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 2 Day 15 | 80.5 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 377 |
| 200 mg Abemaciclib With a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 3 Day 1 | 146 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 174 |
| 200 mg Abemaciclib Without a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 3 Day 1 | 223 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| 200 mg Abemaciclib Without a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 1 Day 15 | 242 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| 200 mg Abemaciclib Without a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 2 Day 15 | 221 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| 200 mg Abemaciclib Without a Meal | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 2 Day 1 | 210 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 57 |
| 200 mg Abemaciclib Without Regard to Food | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 3 Day 1 | 107 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 172 |
| 200 mg Abemaciclib Without Regard to Food | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 2 Day 1 | 152 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 222 |
| 200 mg Abemaciclib Without Regard to Food | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 2 Day 15 | 182 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 112 |
| 200 mg Abemaciclib Without Regard to Food | PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 | Cycle 1 Day 15 | 287 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 63 |