Adj. Dynamic Marker - Adjusted Personalized Therapy Comparing Abemaciclib Combined With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy in (Clinical or Genomic) High Risk, HR+/HER2- EBC
Overview
- Phase
- Phase 3
- Intervention
- Abemaciclib 50 MG; 150mg 1-0-1 per os
- Conditions
- Breast Cancer Female
- Sponsor
- West German Study Group
- Enrollment
- 1260
- Locations
- 85
- Primary Endpoint
- invasive disease-free survival (iDFS)
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
Patients with breast cancer, who have completed first line therapy (e.g., radiotherapy, chemotherapy, surgery), and who have to be identified with having a high risk of recurrence of cancer, will be eligible for the study. This patient group is currently offered a standard of care chemotherapy plus endocrine therapy (ET). The study investigates whether the patient group with high-risk early breast cancer benefits from treatment with the medication abemaciclib in combination with ET compared to ET alone.
Detailed Description
The WSG ADAPT trial program is one of the first new generation trials addressing the issue of individualization of (neo)-adjuvant decision-making in early breast cancer (EBC) in a subtype-specific manner. The first WSG ADAPT umbrella trial (NCT01779206) aimed to establish early predictive molecular surrogate markers for response after a short 3-week induction treatment. The goals of the WSG ADAPT trial program - early response assessment and subtype-specific therapy tailoring to those patients who are most likely to benefit - have contributed to the positive national and international feedback regarding the ADAPT-concept as a whole. The aim of this ADAPTlate phase-III-trial is to gain further knowledge of the group of patients at intermediate to high risk for disease recurrence, who have completed definite locoregional therapy (with or without neoadjuvant or adjuvant chemotherapy). With ADAPTlate it is planned to investigate if the intermediate to high-risk patient group identified during the screening phase derives additional benefit from treatment with abemaciclib in combination with ET compared to ET alone.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A. Prior to REGISTRATION
- •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 allowed screening period can be used for screening of patient).
- •≥ 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 \< 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and/or FSH and estradiol in the postmenopausal range per local normal range.
- •4b. OR: Pre-/perimenopausal patients:
- •confirmed negative serum or urine pregnancy test (β-hCG) before starting study treatment, or
- •patient has had a hysterectomy.
- •Histologically confirmed diagnosis(by local laboratory ) of estrogen-receptor positive and/or progesterone-receptor positive (\>1% ) primary early breast cancer or local relapse. In case the receptor status from local pathology is unclear a central pathology review is obligatory. Results must be known prior to randomization.
Exclusion Criteria
- •Patients eligible for inclusion in this study must not meet any of the following criteria:
- •Patient with distant metastases of breast cancer beyond regional lymph nodes.
- •Previously received CDK 4/6 inhibitor.
- •Patient with a known hypersensitivity to any of the excipients of abemaciclib or standard-of-care endocrine therapy.
- •Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
- •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 is allowed).
- •Patient has a concurrent malignancy or non-breast malignancy within 5 years prior to randomization.
- •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).
- •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.
- •Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator´s judgment, 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.).
Arms & Interventions
Abemaciclib plus ET
Abemaciclib 150 mg, 2 x daily, resulting in 300 mg/day, oral, 24 months plus endocrine treatment of physician´s choice
Intervention: Abemaciclib 50 MG; 150mg 1-0-1 per os
Outcomes
Primary Outcomes
invasive disease-free survival (iDFS)
Time Frame: at end of study, 3-6 years after start of study treatment
superiority in invasive disease-free survival (iDFS) of abemaciclib + endocrine therapy vs. standard-of-care endocrine therapy in patients with HR+/HER2- high risk breast cancer.
Secondary Outcomes
- differences in overall survival (OS) and dDFS(at end of study, 3-6 years after start of study treatment)
- subgroup and multivariable survival analyses(at end of study, 3-6 years after start of study treatment)
- EQ-5D-5L(at end of study, on average 3-6 years after start of treatment)
- EORTC QLQ-C30(at end of study, on average 3-6 years after start of treatment)
- CNS metastases(at end of study, 3-6 years after start of study treatment)
- overall survival (OS)(at end of study, 3-6 years after start of treatment)
- EORTC QLQ-BR23(at end of study, on average 3-6 years after start of treatment)