Description:
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.
Title
- Brief Title: Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer
- Official Title: A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone in Patients With High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
16338
- SECONDARY ID:
I3Y-MC-JPCF
- SECONDARY ID:
2016-004362-26
- SECONDARY ID:
NSABP B-58
- NCT ID:
NCT03155997
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Abemaciclib | LY2835219 | 150 mg Abemaciclib + Endocrine Therapy |
| Standard Adjuvant Endocrine Therapy | | 150 mg Abemaciclib + Endocrine Therapy |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 150 mg Abemaciclib + Endocrine Therapy | Experimental | 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. | - Abemaciclib
- Standard Adjuvant Endocrine Therapy
|
| Endocrine Therapy | Other | Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met. | - Standard Adjuvant Endocrine Therapy
|
Eligibility Criteria
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Invasive Disease Free Survival (IDFS) |
| Time Frame: | Baseline to Recurrence or Death from Any Cause (Up to 32 Months) |
| Safety Issue: | |
| Description: | 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
| Measure: | IDFS for Participants With Ki-67 Index ≥20% |
| Time Frame: | Baseline to Recurrence or Death from Any Cause (Approximately 10 Years) |
| Safety Issue: | |
| Description: | Outcome data will be provided after the study is completed. |
| Measure: | Distant Relapse-Free Survival (DRFS) |
| Time Frame: | Baseline to Distant Recurrence or Death from Any Cause (Up to 32 Months) |
| Safety Issue: | |
| Description: | Distant relapse-free survival is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first. |
| Measure: | Overall Survival (OS) |
| Time Frame: | Baseline to Death from Any Cause (Approximately 10 Years) |
| Safety Issue: | |
| Description: | Outcome data will be provided after the study is completed. |
| Measure: | Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib |
| Time Frame: | Day 1 (2 hours post-dose), Days 30, 60, 90 post-dose |
| Safety Issue: | |
| Description: | Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib |
| Measure: | Change From Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B) |
| Time Frame: | Baseline, Follow Up (Approximately 3 Years) |
| Safety Issue: | |
| Description: | Outcome data will be provided after the study is completed. |
| Measure: | Change From Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) |
| Time Frame: | Baseline, Follow Up (Approximately 3 Years)] |
| Safety Issue: | |
| Description: | Outcome data will be provided after the study is completed. |
| Measure: | Change From Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) |
| Time Frame: | Baseline, Follow Up (Approximately 3 Years)] |
| Safety Issue: | |
| Description: | Outcome data will be provided after the study is completed. |
| Measure: | Change From Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) |
| Time Frame: | Baseline, Follow Up (Approximately 3 Years)] |
| Safety Issue: | |
| Description: | Outcome data will be provided after the study is completed. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Eli Lilly and Company |
Trial Keywords
- early stage breast cancer
- cyclin-dependent kinase (CDK)
Last Updated
April 9, 2021
