A Neoadjuvant Study of Abemaciclib (LY2835219) in Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Breast Cancer
- Conditions
- Breast CancerEarly-Stage Breast CarcinomaHormone Receptor Positive Tumor
- Interventions
- Registration Number
- NCT02441946
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to evaluate the biological effects of abemaciclib in combination with anastrozole and compare those to the effects of abemaciclib alone and anastrozole alone in the tumors of postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 224
- Have postmenopausal status.
- Adenocarcinoma of the breast.
- Breast tumor ≥1 centimeter (cm) in diameter, HR+, HER2-.
- Neoadjuvant endocrine monotherapy is deemed to be a suitable therapy.
- Primary breast cancer that is suitable for baseline core biopsy.
- Have adequate organ function.
- Bilateral invasive breast cancer.
- Metastatic breast cancer (local spread to axillary lymph nodes is permitted).
- Inflammatory breast cancer.
- Prior systemic therapy or radiotherapy for invasive or non-invasive breast cancer in the same breast as currently being treated.
- Prior radiotherapy to the ipsilateral chest wall for any malignancy.
- Prior anti-estrogen therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Abemaciclib + Anastrozole Abemaciclib Abemaciclib (150 milligrams \[mg\]) was given orally every 12 hours (Q12H) plus anastrozole (1 mg) orally once daily (QD) for 2 weeks. Loperamide was given as a prophylaxis for 4 weeks and then at physician discretion. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Total treatment duration was 16 weeks. Abemaciclib + Anastrozole Loperamide Abemaciclib (150 milligrams \[mg\]) was given orally every 12 hours (Q12H) plus anastrozole (1 mg) orally once daily (QD) for 2 weeks. Loperamide was given as a prophylaxis for 4 weeks and then at physician discretion. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Total treatment duration was 16 weeks. Abemaciclib + Anastrozole Anastrozole Abemaciclib (150 milligrams \[mg\]) was given orally every 12 hours (Q12H) plus anastrozole (1 mg) orally once daily (QD) for 2 weeks. Loperamide was given as a prophylaxis for 4 weeks and then at physician discretion. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Total treatment duration was 16 weeks. Abemaciclib Loperamide Abemaciclib (150 mg) was given orally Q12H for 2 weeks. Loperamide was given as a prophylaxis for 4 weeks and then at physician discretion. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Total treatment duration was 16 weeks. Abemaciclib Abemaciclib Abemaciclib (150 mg) was given orally Q12H for 2 weeks. Loperamide was given as a prophylaxis for 4 weeks and then at physician discretion. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Total treatment duration was 16 weeks. Anastrozole Abemaciclib Anastrozole (1 mg) is given orally QD for 2 weeks. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Loperamide was given as a prophylaxis for the first 2 weeks of the combination treatment and then at physician discretion. Total treatment duration was 16 weeks. Abemaciclib Anastrozole Abemaciclib (150 mg) was given orally Q12H for 2 weeks. Loperamide was given as a prophylaxis for 4 weeks and then at physician discretion. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Total treatment duration was 16 weeks. Anastrozole Loperamide Anastrozole (1 mg) is given orally QD for 2 weeks. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Loperamide was given as a prophylaxis for the first 2 weeks of the combination treatment and then at physician discretion. Total treatment duration was 16 weeks. Anastrozole Anastrozole Anastrozole (1 mg) is given orally QD for 2 weeks. All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Loperamide was given as a prophylaxis for the first 2 weeks of the combination treatment and then at physician discretion. Total treatment duration was 16 weeks.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline to 2 Weeks in Ki67 Expression Baseline, 2 Weeks Tumor tissue collected through a core biopsy at baseline and at the end of cycle 1 was used to determine Ki67 expression. Ki67 expression is defined as the percent of cells staining positive by validated central assay.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Pathologic Complete Response (pCR) From Start of Treatment Up to 16 Weeks pCR is defined as absence of invasive cancer in the breast and sampled regional lymph nodes.
Percentage of Participants With Complete Response (CR) or Partial Response (PR): Clinical Objective Response From Start of Treatment to Objective Progression or Start of New Anticancer Therapy (Up to 16 Weeks) Clinical objective response is defined as the percentage of participants with the best overall response rate (ORR) with a best OR of CR or PR, according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1. ORR is recorded from the start of the study treatment until the earliest of objective progression or start of new anticancer therapy. A responder depends on target and non-target disease and the appearance of new lesions. CR is defined as the disappearance of all non-target lesions. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. All lymph nodes are non-pathological or normal in size (\<10mm short axis). Progressive disease (PD) is a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, a relative increase of 20%, the sum must also demonstrate an absolute increase of 5 mm.
Percentage of Participants With Complete Radiologic Response or Partial Radiological Response: Radiological Response From Start of Treatment to Objective Progression or Start of New Anticancer Therapy (Up to 16 Weeks) Radiological response is the percentage of participants with CR or, PR according to RECIST v.1.1. A responder is defined as any participant who exhibits a CR or PR. CR is the disappearance of all target lesions. PR is a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. PD is 20% increase in the sum of diameters of target lesions taking as reference the smallest sum and the appearance of 1 or more new lesions.
Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Baseline, 2 Weeks EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, emotional, cognitive, or social functioning), global health status and symptom scales of fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.
Pharmacokinetics (PK): Apparent Clearance of Abemaciclib Cycle(C)1, Day(D)1: 2 to 4 Hours (Hrs) Postdose; C1D14: 4 Hrs Postdose, 7 Hrs Postdose; C3D1: Predose, 3 Hrs Postdose, C4D1 & C5D1, Predose, C5D28: Predose, 3 Hrs Postdose Abemaciclib apparent clearance (CL/F) was calculated by population nonlinear mixed effects modeling (NONMEM) using all available data spanning cycles 1 and cycles 3-5.
PK: Apparent Volume of Distribution of Abemaciclib Cycle(C)1, Day(D)1: 2 to 4 Hours (Hrs) Postdose; C1D14: 4 Hrs Postdose, 7 Hrs Postdose; C3D1: Predose, 3 Hrs Postdose, C4D1 & C5D1, Predose, C5D28: Predose, 3 Hrs Postdose Abemaciclib apparent volume of distribution was calculated by population NONMEM using all available data spanning cycles 1 and cycles 3-5.
Trial Locations
- Locations (31)
Millennium Oncology
🇺🇸Houston, Texas, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
🇨🇳Taipei, Taiwan
Holy Cross Hospital Inc.
🇺🇸Fort Lauderdale, Florida, United States
Memorial Regional Hospital/Joe Dimaggio Childrens Hospital
🇺🇸Hollywood, Florida, United States
SMO TRIO -Translational Research
🇺🇸Los Angeles, California, United States
University of California-San Diego
🇺🇸La Jolla, California, United States
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Sansum Medical Research Foundation
🇺🇸Santa Barbara, California, United States
Central Coast Medical Oncology Corporation
🇺🇸Santa Monica, California, United States
Stanford University
🇺🇸Stanford, California, United States
St Mary's Hospital Regional Cancer Center
🇺🇸Grand Junction, Colorado, United States
Florida Cancer Research Institute
🇺🇸Plantation, Florida, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇰🇷Seongnam, Korea, Republic of
Nebraska Hematology-Oncology
🇺🇸Lincoln, Nebraska, United States
The West Clinic
🇺🇸Germantown, Tennessee, United States
Kaiser Foundation Hospitals
🇺🇸Honolulu, Hawaii, United States
Cancer Care Associates Medical Group
🇺🇸Redondo Beach, California, United States
Northeast Georgia Cancer Care, LLC
🇺🇸Athens, Georgia, United States
University of Massachusetts Medical Center
🇺🇸Worcester, Massachusetts, United States
St. Charles Health System
🇺🇸Bend, Oregon, United States
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
🇨🇦Ottawa, Canada
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
🇰🇷Songpa-gu, Korea, Republic of
Columbia Basin Hematology & Oncology
🇺🇸Kennewick, Washington, United States
Georgia Regents University
🇺🇸Augusta, Georgia, United States
SMO Pharmatech Oncology Inc
🇺🇸Denver, Colorado, United States
Oncology and Radiation Associates
🇺🇸Miami, Florida, United States
Orlando Health, Inc
🇺🇸Orlando, Florida, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States