Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10006199 Term: Breast cancer stage I System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1]Female (regardless of menopausal status) or male =18 years of age [2]The patient has confirmed HR+, HER2-negative (HER2-), early stage resected invasive breast cancer without evidence of distant metastases [3]The patient must have undergone definitive surgery of the primary breast tumor(s) [4]The patient must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization. [5]Patients must be node positive and fulfill one of the following criteria: A. pathological tumor involvement in =4 ipsilateral axillary lymph nodes. OR B. Pathological tumor involvement in 1 to 3 ipsilateral axillary lymph node(s) and meet at least 1 of the following criteria: Grade 3, pathological primary invasive tumor size =5 cm, Ki-67 index of =20% (for Cohort 2) on untreated breast tissue [6] The patient must be randomized within 16 months from the time of definitive breast cancer surgery [7]If the patient is currently receiving or initiating standard adjuvant endocrine therapy at time of study entry, she/he may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation), whichever is last. [8] Patients who received or will be receiving adjuvant chemotherapy must have completed adjuvant chemotherapy prior to randomization and patients must have recovered from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. Patients who are not candidates for adjuvant chemotherapy or decline chemotherapy are permitted. Patients may also have received neoadjuvant chemotherapy. A washout period of at least 21 days is required between last adjuvant chemotherapy dose and randomization. [9] Patients who received or will be receiving adjuvant radiotherapy must have completed radiotherapy prior to randomization, and patients must have recovered (Grade =1) from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization. [10] The patient has recovered from surgical side effects following definitive breast surgery based on investigator discretion. [11] Women of reproductive potential must have a negative blood pregnancy test at baseline and agree to use highly effective contraceptive methods to prevent pregnancy during the study and for 12 weeks following the last dose of study treatment. Males must agree to use an acceptable method of birth control and to not donate sperm during the study and for at least 12 weeks following the last dose of study treatment. [12]The patient has a ECOG performance status =1 [13]The patient has adequate organ function [14]The patient is able to swallow oral medications [15]The patient has given written informed consent prior to any study-specific procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2290 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2290
Exclusion criteria
Exclusion criteria: [1]The patient has metastatic disease or lymph node-negative breast cancer. Patients with inflammatory breast cancer are excluded. [2]Patients with a history of previous breast cancer are excluded, with the exception of ipsilateral DCIS treated by locoregional therapy alone =5 years ago. Patients with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Patients 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. [3]Females who are pregnant or lactating. [4]The patient has previously received treatment with any CDK4 and CDK6 inhibitor. [5]The patient is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate). [6]The patient has previously received endocrine therapy for breast cancer prevention (tamoxifen or raloxifene or aromatase inhibitors). [7]The patient has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study, such as severe renal impairment, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in clinically significant diarrhea. [8]The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin. [9]The patient has active systemic infections or viral load. [10]The patient has had major surgery within 14 days prior to randomization. [11]The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to randomization, or is currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy, in terms of IDFS, for patients with HR+, HER2- early stage breast cancer for abemaciclib plus adjuvant endocrine therapy versus adjuvant endocrine therapy alone.;Secondary Objective: To evaluate the efficacy, in terms of IDFS, for patients with HR+, HER2- early stage breast cancer with pretreatment Ki-67 index =20% by central lab To evaluate the efficacy of abemaciclib plus adjuvant endocrine therapy versus adjuvant endocrine therapy alone in terms of DRFS and OS To assess the safety profile To evaluate the relationship between abemaciclib, exposure and clinical outcomes To evaluate abemaciclib plus adjuvant endocrine therapy, versus adjuvant endocrine therapy alone, in terms of general oncology and breast cancer self-reported health-related quality of life, endocrine therapy-specific symptoms and fatigue experienced during abemaciclib and/or endocrine therapy. To evaluate health status using the EQ-5D-5L. ;Primary end point(s): To compare invasive disease free survival (IDFS) for patients receiving adjuvant endocrine therapy plus abemaciclib treatment versus adjuvant endocrine therapy alone in HR+, HER2- breast cancer.;Timepoint(s) of evaluation of this end point: After 5 years when approximately 390 events have occured. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The Invasive Disease-Free Survival (IDFS), for patients with HR+, HER2- early stage breast cancer with pretreatment Ki-67 index =20% (by central lab) •Efficacy endpoints: distant relapse-free survival (DRFS), overall survival (OS) •Safety endpoints will include but are not limited to the following: TEAEs, SAEs, and hospitalizations Clinical laboratory tests, vital signs, and physical examinations •Steady-state trough abemaciclib concentration (Cmin,ss), hazard ratio for IDFS, DRFS, OS, other efficacy and safety endpoints •Composite and single-item endpoints will be evaluated to examine differentiating effects of abemaciclib across study arms. Measurement will be undertaken using the FACT-B questionnaire for general oncology and breast cancer health-related quality of life; the FACT-ES subscale and additional FACIT-sourced items for cognitive and bladder endocrine therapy symptoms; and the FACIT-F subscale to characterize this symptom know to be associated with oncology, endocrine therapy, and abemaciclib treatment. •The EQ-5D-5L health state profile (the index score and the single-item health status measure) will be used to inform decision modeling for economic evaluations and this questionnaire will be coadministered with and after first completing the FACT/FACIT questionnaire, subscales, and additional items. ;Timepoint(s) of evaluation of this end point: After approximately 5 years when approximately 390 events have occured. At the end of trial. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Singapore, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed