HR+/HER2- early breast cancer
Conditions
Interventions
Trade Name: Verzenios
Product Name: Verzenios
Product Code: LY2835219
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Abemaciclib
Current Sponsor code: LY2835219
Other descriptive name: A
Sponsors
Westdeutsche Studiengruppe GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent prior to any study procedures (outcomes of standard-of-care procedures performed before signing of informed consent by the patient but within the allowed screening period can be used for patient screening). 2. Female. 3. = 18 years of age. 4a. EITHER: (Post)menopausal status at the time of initiation of adjuvant study medication • patient underwent bilateral oophorectomy, or • age = 60, or • age 1%) early breast cancer by local laboratory. In case the receptor status from local pathology is unclear a central pathology review is obligatory. Results must be known prior to randomization. 6. Patient has HER2-negative breast cancer defined as • a negative in-situ hybridization test or an IHC status of 0, 1+, or 2+, • if IHC is 2+, a negative in-situ hybridization (FISH, CISH, or SISH) test is required (based on the analyzed tissue sample at initial diagnosis by a local laboratory). 7. Patients are eligible • with completed (i.e., 5 years according to SoC), planned or ongoing adjuvant endocrine therapy, without any signs of distant relapse or secondary malignancy AND • if primary diagnosis was 6 years or less before enrollment 8a. Known high clinical risk, in case of neoadjuvant chemotherapy, defined as either one of the following criteria: see protocol Known high clinical risk, in case of adjuvant treatment (chemotherapy and/or ET), defined as either one of the following criteria: see protocol OR 8b. Known high genomic risk, defined as either one of the following criteria: see protocol NOTE: In case of neoadjuvant chemotherapy treatment: participation of non-pCR patients is strongly recommended OR In case the tumor is of intermediate clinical risk, but genomic risk is not known at registration: 8c. Intermediate clinical and unknown genomic risk, c or yp/pN 0 with luminal-B-like tumor (G3 and/or Ki-67 pre-treatment = 20%) or c or yp/pN 1, AND (see protocol) NOTE: In case of neoadjuvant chemotherapy treatment: participation of non-pCR patients is strongly recommended OR 8d Patients after isolated locoregional relapse with high-risk patterns (e.g., T2-3 or N1-3 or G3 or Ki-67 pre-treatment = 20%), once surgery with free margins was completed Inclusion is only possible for the first locoregional relapse removed by surgery (free margins) 9. Completed primary therapy of breast cancer according to current guidelines, i.e., after (neo)adjuvant treatment, definite surgery and radiotherapy, if applicable. 10. No clinical evidence of distant metastasis (confirmation recommended prior to randomization by either combination of or either one of the following examinations: CT thorax / abdomen, chest X-ray, liver ultrasound, bone scan, PET-CT). 11. Patient has available tumor tissue from primary diagnostic biopsy. 12. No contraindication for adjuvant ET. 13. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 14. Patient has adequate bone marrow and organ function as defined by the following laboratory values: see protocol 15. Ability to swallow abe
Exclusion criteria
Exclusion criteria: Patients eligible for inclusion in this study must not meet any of the following criteria: 1. Patient with distant metastases of breast cancer beyond regional lymph nodes. 2. Previously received CDK 4/6 inhibitor or patient with an indication for abemaciclib in the clinical routine per respective country: • N 2-3 or • N 1 and at least one of the following criteria: G3 or T3 and • <14 months after primary diagnosis 3. Patient with a known hypersensitivity to any of the excipients of abemaciclib or standard-of-care endocrine therapy. 4. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects. 5. Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 5.0 Grade = 1 (polyneuropathy = 2 or residual alopecia is allowed). 6. Patient has a concurrent malignancy or non-breast malignancy within 5 years prior to randomization. 7. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small-bowel resection). 8. Patient has any active systemic bacterial infection (requiring intravenous antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment. 9. Patient has any other concurrent severe and/or uncontrolled medical condition that, in the investigator´s judgment, could cause unacceptable safety risks, contraindicate patient participation in the clinical study, or compromise compliance with the protocol (e.g., interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], 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 baseline Grade 2 or higher diarrhea, etc.). 10. Patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. 11. Patient is currently receiving any of the following substances, which cannot be discontinued 7 days prior to day 1 of study treatment: - concomitant medications and herbal supplements, that are strong inducers or inhibitors of CYP3A4. 12. Participation in a prior investigational study within 30 days prior to enrollment.. 13. Not able to understand and to comply with study instructions and requirements. 14. Pregnant or nursing (lactating) woman. 15. Woman of child-bearing potential defined as woman physiologically capable of becoming pregnant, unless she is using highly effective methods of contraception during the study treatment and for 21 days after stopping the treatment: a. total abstinence (when this is in line with the preferred and usual lifestyle of the patient), b. female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment, c. male partner s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate superiority in invasive disease-free survival (iDFS) of abemaciclib + ET vs. standard ET. ;Secondary Objective: Assessment of •overall survival (OS) and distant DFS (dDFS) in both arms, •differences in OS and dDFS, •subgroup and multivariable survival analyses, •occurrence of central nervous system (CNS) metastases, •patient reported outcomes, quality of life (EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5L), •translational research.;Primary end point(s): Invasive disease-free survival (iDFS) is defined as the length of time after date of randomization (excluded) that the patient survives until development of any invasive cancer event, confirmed by histology or clinical diagnosis (e.g., first description by imaging) or death of any cause.;Timepoint(s) of evaluation of this end point: Timepoint of progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessment of • iDFS since primary diagnosis • OS and dDFS since randomization, • OS and dDFS since primary diagnosis, • occurrence of CNS metastases since randomization, • occurrence of CNS metastases since primary diagnosis, • subgroup and multivariable survival analyses defined by key clinical, genomic, and endocrine response parameters, • patient reported outcomes, quality of life (EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5L), • Efficacy of therapy according to distinct clinical and biological (measured by genomic signatures and other markers) prognostic subgroups.;Timepoint(s) of evaluation of this end point: End of study for each patient | — |
Countries
Germany
Contacts
Public ContactClinical Trial Information Desk
iOMEDICO AG
Outcome results
None listed