Abemaciclib Dose Escalation to Maintain Intensity (ADE-MI)

Study Overview
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Brief Summary
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This is a post-marketing single arm, phase IV trial in which patients with high-risk early-stage HR+HER2- breast cancer will receive adjuvant abemaciclib in combination with endocrine therapy (ET) After study intervention, participants will remain on combination abemaciclib + ET at the discretion of their treating providers

Detailed Description
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Dose escalation (DE) was shown to minimize the rates of Grade 3 diarrhea in the setting for HER2+ breast cancer. DE can improve tolerability for drugs such as abemaciclib. This is a post-marketing single arm, phase IV trial in which patients with high-risk early-stage HR+HER2- breast cancer will receive adjuvant abemaciclib in combination with endocrine therapy (ET) After study intervention, participants will remain on combination abemaciclib + ET at the discretion of their treating providers In this study, the investigators we will test the hypothesis that gradual up-titration of abemaciclib dose over a course of 3-4 weeks will decrease the rate of G3 or worse diarrhea, permitting more patients to remain at the intended dose when evaluated at day 84

Official Title
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Abemaciclib Dose Escalation to Maintain Intensity (ADE-MI)

Conditions
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Breast Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG 0-2 Histologically confirmed early-stage HR+HER2- breast cancer documented by biopsy who are prescribed adjuvant abemaciclib Able to provide written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization. Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required per institutional practice guidelines. As determined at the discretion of the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. Exclusion Criteria: Chronic history of diarrhea Active infection requiring systemic therapy Uncontrolled HIV/AIDS or active viral hepatitis Pregnant or nursing Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen, as determined by the treating medical oncologist. Other major comorbidity as determined by study PI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Abemaciclib|Week 1 50mg orally BID|
|Drug: Abemaciclib|Week 2 100mg orally BID|
|Drug: Abemaciclib|Week 3 150mg orally QAM, 100mg orally QHS|
|Drug: Abemaciclib|Week 4 150mg orally BID|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase the proportion of subjects on FDA approved dose of Abemaciclib (150mg BID) at day 84 | Number of subjects that continue to receive Abemaciclib 150mg BID for 84 days | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| How many days with Grade 2 or greater of diarrhea in the first month | Number of days with Grade 2 or greater in the first month | 1 month | 
| Rate of Grade 3 or greater of diarrhea in the first 3 months | Nuber of subjects who experienced Grade 3 or greater by the total number of subjects enrolled | 3 months | 
| Disease Free Survival (DFS) | Number of subjects that have DFS from D1 of treatment until the criteria for disease progression as defined by RECIST 1.1 or death | 1 year | 
| Disease Free Survival (DFS) | Number of subjects that have DFS from D1 of treatment until the criteria for disease progression as defined by RECIST 1.1 or death | 2 years | 
| Overall Survival (OS) | OS is defined as the time from D1 of treatment until death | 1 year | 
| Overall Survival (OS) | OS is defined as the time from D1 of treatment until death | 2 years | 
| Overall Survival (OS) | OS is defined as the time from D1 of treatment until death | 3 years | 
| Subject reported outcomes regarding adverse events | Toxicity grade as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | 5 years |