A Study of Abemaciclib (LY2835219) With and Without Food in Participants With Metastatic Breast Cancer

Study Overview
=================
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.

Official Title
-----------------
An Open-Label, Randomized Phase 2 Study of the Impact of Food on Tolerability When Receiving Abemaciclib for Patients With Previously Treated Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer

Conditions
-----------------
Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: Abemaciclib


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 200 mg Abemaciclib With a Meal<br>200 mg abemaciclib given twice a day (BID) orally with a meal. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;|
| Experimental: 200 mg Abemaciclib Without a Meal<br>200 mg abemaciclib given twice a day (BID) orally without a meal, taken in the modified fasted condition. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;|
| Experimental: 200 mg Abemaciclib Without Regard to Food<br>200 mg abemaciclib given twice a day (BID) orally without regard for food. | Drug: Abemaciclib<br>* Administered orally.<br>* Other names: LY2835219;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Cycle 3 (28 Days Cycle) | 
| 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. | Cycle 3 (28 Days Cycle) | 
| Percentage of Participants With Dose Reductions Due to Diarrhea | Percentage of participants with dose reductions due to diarrhea during first 3 cycles. | Cycle 3 (28 Days Cycle) | 
| Percentage of Participants With Dose Interruptions Due to Diarrhea | Percentage of participants with dose interruptions due to diarrhea during first 3 cycles. | Cycle 3 (28 Days Cycle) | 
| Percentage of Participants Who Discontinue Treatment Due to Diarrhea | Percentage of participants who discontinue treatment due to diarrhea | Cycle 3 (28 Days Cycle) | 
| Percentage of Participants Utilizing Antidiarrheals | Percentage of participants who utilized anti diarrheals at least once during the first 3 cycles. | Cycle 3 (28 Days Cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib | 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 Metabolite LSN2839567 | 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 LSN3106726 | 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) |