Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer

Phase 3

Active, not recruiting

Conditions: Breast Cancer

Interventions: Drug: Abemaciclib
Drug: Standard Adjuvant Endocrine Therapy

Registration Number: NCT03155997

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 5637

Inclusion Criteria

Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations).
The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases.
The participant must have undergone definitive surgery of the primary breast tumor.
The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization.
Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence:
- 4 or more positive axillary lymph nodes
- Tumor size of at least 5 centimeters
- Grade 3 defined as at least 8 points on the Bloom Richardson grading system
- Ki-67 index by central analysis of ≥20% on untreated breast tissue
The participant must be randomized within 16 months from the time of definitive breast cancer surgery.
The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last.
Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery.
Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods.
The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
The participant has adequate organ function.
The participant is able to swallow oral medications.

Exclusion Criteria

Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease.
Participants with inflammatory breast cancer.
Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a 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 5 years from the date of randomization are excluded.
Females who are pregnant or lactating.
The participant has previously received treatment with any CDK4 and CDK6 inhibitor.
The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate).
The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene.
The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE).
The participant has active systemic infections or viral load.
The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
150 mg Abemaciclib + Endocrine Therapy	Standard Adjuvant Endocrine Therapy	Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.
Endocrine Therapy	Standard Adjuvant Endocrine Therapy	Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.
150 mg Abemaciclib + Endocrine Therapy	Abemaciclib	Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.

Primary Outcome Measures

Name	Time	Method
Invasive Disease Free Survival (IDFS)	Baseline to Recurrence or Death from Any Cause (Up to 32 Months)	IDFS, as defined by the STEEP System, was 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)	Baseline, Follow Up (Approximately 3 Years)]	Outcome data will be provided after the study is completed.
Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib	Day 1 (2 hours post-dose), Days 30, 60, 90 post-dose	Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib
Change From Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B)	Baseline, Follow Up (Approximately 3 Years)	Outcome data will be provided after the study is completed.
IDFS for Participants With Ki-67 Index ≥20%	Baseline to Recurrence or Death from Any Cause (Approximately 10 Years)	Outcome data will be provided after the study is completed.
Change From Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES)	Baseline, Follow Up (Approximately 3 Years)]	Outcome data will be provided after the study is completed.
Distant Relapse-Free Survival (DRFS)	Baseline to Distant Recurrence or Death from Any Cause (Up to 32 Months)	Distant relapse-free survival is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first.
Overall Survival (OS)	Baseline to Death from Any Cause (Approximately 10 Years)	Outcome data will be provided after the study is completed.
Change From Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L)	Baseline, Follow Up (Approximately 3 Years)]	Outcome data will be provided after the study is completed.

Trial Locations

Locations (605): Millennium Oncology - Hollywood
🇺🇸
Hollywood, Florida, United States
Renown Regional Medical Center
🇺🇸
Reno, Nevada, United States
The Valley Hospital, Inc.
🇺🇸
Paramus, New Jersey, United States
The West Clinic, PLLC dba West Cancer Center
🇺🇸
Germantown, Tennessee, United States
IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas
🇦🇷
Buenos Aires, Argentina
Instituto Alexander Fleming
🇦🇷
Ciudad Autónoma de Buenos Aires, Argentina
Epworth Hospital
🇦🇺
East Melbourne, Victoria, Australia
St John of God Subiaco Hospital
🇦🇺
Subiaco, Western Australia, Australia
Université Catholique de Louvain-Namur - Centre Hospitalier Universitaire Dinant-Godinne - Site Godinne
🇧🇪
Yvoir, Namur, Belgium
AZ Nikolaas
🇧🇪
Sint-Niklaas, Oost-Vlaanderen, Belgium
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Millennium Oncology - Hollywood
🇺🇸Hollywood, Florida, United States