Adjuvant Therapy With Abemaciclib + SOC ET vs. SOC ET in Clinical or Genomic High Risk, HR+/HER2- EBC

NCT ID: NCT04565054

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-02
• Study Completion Date: 2029-07-31

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.

Conditions

Breast Cancer Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Abemaciclib plus ET

Abemaciclib 150 mg, 2 x daily, resulting in 300 mg/day, oral, 24 months plus endocrine treatment of physician´s choice

Group Type: EXPERIMENTAL

Abemaciclib 50 MG; 150mg 1-0-1 per os

Intervention Type: DRUG

Experimental: Abemaciclib plus ET Abemaciclib 150 mg, 2 x daily, resulting in 300 mg/day, oral, 24 months plus endocrine treatment of physician´s choice

Standard-of-care ET

Standard-of-care ET according to clinical guidelines.

Pre-/perimenopausal patients:

• Either aromatase inhibitor + GnRH agonist
• or Tamoxifen +/- GnRH-agonist (as per investigator´s decision) or

Postmenopausal patients:

• Either Aromatase inhibitor
• or Tamoxifen OR

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Abemaciclib 50 MG; 150mg 1-0-1 per os

Experimental: 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 Type: DRUG

Other Intervention Names

Verzenios

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). 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 < 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. 5. 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.

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. Intermediate to high clinical or genomic risk, defined as either one of the following criteria:
• c or p or ypN 2-3 with/without (neo)adjuvant chemotherapy;
• in patients with c/ypN0-1:
• non-pCR in patients with G3 or c/ypN1
• high biological risk defined as G3 with Ki-67 ≥40%
• or high genomic risk (RS>25 (known or Oncotype Dx® in screening phase) or another test)
• high CTS5 score or UICC stage IIb (clinical if neoadjuvant chemotherapy or pathological)

OR, if patients do not fulfill above criteria:

• patients ≤50 years old or pre-/perimenopausal and c or (y)pN1 disease (in particular if ET-non-response or no chemotherapy)
• patients >50 years old and postmenopausal and c or (y)pN1 with intermediate genomic risk (RS≥18) or non-low risk by another test

ET non-response definition:

Ki-67 post-treatment > 10% (central or local pathology value) OR 8b. Patients after isolated locoregional relapse with high-risk patterns (e.g., rpT2-3 or rpN1-3 or G3 or Ki-67 pre-treatment ≥20%), once surgery with free margins was completed Note: Inclusion is only possible for the first locoregional relapse removed by surgery (free margins) OR 8c. Patients with any high clinical risk at Investigator´s assessment but not fulfilling above criteria: consultation with sponsor required

B. Prior to RANDOMIZATION in the study 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:

• absolute neutrophil count ≥ 1.5 × 109/L,
• platelets ≥ 100 × 109/L,
• hemoglobin ≥ 8.0 g/dL,
• total bilirubin ≤ 1.5 ULN, except for patients with Gilbert's Syndrome who may only be included if the total bilirubin is ≤ 2.0 × ULN or direct bilirubin within normal ranges,
• aspartate transaminase (AST) ≤ 3 × ULN,
• alanine transaminase (ALT) ≤ 3 × ULN,
• serum creatinine ≤ 1.5 x ULN. 15. Ability to swallow abemaciclib tablets or to administer other study medication, respectively.

16. Ability to communicate with the investigator and comply with study procedures.

17. Willing to receive therapy by clinical site, as required by the protocol.

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.

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 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 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.).

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:

o 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:

1. total abstinence (when this is in line with the preferred and usual lifestyle of the patient).

2. female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment.

3. male partner sterilization (at least 6 months prior to study screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.

4. placement of an intrauterine device (IUD).

5. use of condom + spermicide.

16. Use of oral (estrogen and progesterone), transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Genomic Health®, Inc.

INDUSTRY

Sponsor Role: collaborator

West German Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Oleg Gluz, PD Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Westdeutsche Studiengruppe GmbH

Locations

Praxis für interdisziplinäre Onkologie & Hämatologie

Freiburg im Breisgau, Baden-Wurttemberg, Germany

SLK Kliniken Heilbronn Klinik für Gynäkologie und Geburtshilfe

Heilbronn, Baden-Wurttemberg, Germany

MVZ für Hämatologie und Onkologie

Ravensburg, Baden-Wurttemberg, Germany

Universitätsklinikum Ulm Frauenheilkunde, Geburtshilfe

Ulm, Baden-Wurttemberg, Germany

GRN-Klinik Weinheim Gynäkologie und Geburtshilfe

Weinheim, Baden-Wurttemberg, Germany

Klinikum Mittelbaden Balg

Baden-Baden, Baden-Würtemberg, Germany

Universitätsklinikum Tübingen Department für Frauengesundheit, Brustzentrum

Tübingen, Baden-Wüttenburg, Germany

Haematologie-Onkologie im Zentrum MVZ GmbH

Augsburg, Bavaria, Germany

Klinikum der Universität München Campus Großhadern Frauenheilunde und Geburtsklinik

Munich, Bavaria, Germany

Medizinisches Zentrum für Hämatologie und Onkologie München MVZ GmbH

Munich, Bavaria, Germany

Rotkreuzkliniken München, Interdisziplinbäres Brustzentrum

München, Bavaria, Germany

Hämatologisch-Onkologische Schwerpunktpraxis Würzburg & Kitzingen

Würzburg, Bavaria, Germany

Medizinische Universität Lausitz - Carl-Thiem Frauenklinik

Cottbus, Brandenburg, Germany

Klinikum Ernst von Bergmann gGmbH Brustzentrum

Potsdam, Brandenburg, Germany

Centrum für Hämatologie und Onkologie

Frankfurt a.M., Hesse, Germany

Brustzentrum, Elisabeth-Krankenhaus gGmbH

Kassel, Hesse, Germany

Gemeinschaftspraxis für Hämatologie und Onkologie

Langen, Hesse, Germany

St. Josefs-Hospital Wiesbaden GmbH Ambulanz der Frauenklinik, Brustzentrum

Wiesbaden, Hesse, Germany

Studien GbR Braunschweig Dr. Lorenz/Dr. Kreiss-Sender

Braunschweig, Lower Saxony, Germany

MVZ II der Niels Stensen Kliniken Onkologie u. Hämatologie

Georgsmarienhütte, Lower Saxony, Germany

MVZ Onkologische Kooperation Harz (GbR)

Goslar, Lower Saxony, Germany

Diakovere Krankenhaus gGmbH Henriettenstift Frauenklinik

Hanover, Lower Saxony, Germany

Medizinische Hochschule Hannover Frauenheilkunde

Hanover, Lower Saxony, Germany

MVM Medizinische Verwaltungs und Managementgesellschaft mbH

Leer, Lower Saxony, Germany

Pius-Hospital Oldenburg Hämatologie, Onkologie

Oldenburg, Lower Saxony, Germany

Klinikum Südstadt Rostock Frauenklinik

Rostock, Mecklenburg-Vorpommern, Germany

Stiftung Katholisches BrustCentrum Marienhospital

Aachen, North Rhine-Westphalia, Germany

Uniklinik RWTH Aachen Gynäkologie und Geburtsmedizin

Aachen, North Rhine-Westphalia, Germany

Evangelisches Krankenhaus Bergisch Gladbach gGmbH Brustzentrum,

Bergisch Gladbach, North Rhine-Westphalia, Germany

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, North Rhine-Westphalia, Germany

Gynäkologisches Zentrum Bonn PD Dr. med. Christian Kurbacher

Bonn, North Rhine-Westphalia, Germany

GYNONOVA GbR Schwerpunktpraxis für gynäkologische Onkologie

Cologne, North Rhine-Westphalia, Germany

St. Elisabeth-Krankenhaus GmbH, Brustzentrum - Senologie

Cologne, North Rhine-Westphalia, Germany

Kliniken der Stadt Köln Krankenhaus Köln-Holweide Medizinische Klinik Brustzentrum

Cologne, North Rhine-Westphalia, Germany

Universitätsklinikum Düsseldorf Frauenheilkunde und Geburtshilfe

Düsseldorf, North Rhine-Westphalia, Germany

MVZ Medical Center Duesseldorf GmbH Luisenkrankenhaus Brustzentrum

Düsseldorf, North Rhine-Westphalia, Germany

St.-Antonius-Hospital Eschweiler Hämatologie/Onkologie

Eschweiler, North Rhine-Westphalia, Germany

Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum

Essen, North Rhine-Westphalia, Germany

Universitätsklinikum Essen Frauenheilkunde und Geburtshilfe

Essen, North Rhine-Westphalia, Germany

Onkodok GmbH Onkologische Schwerpunktpraxis

Gütersloh, North Rhine-Westphalia, Germany

Praxisgemeinschaft Gynäkologische Onkologie & Spezielle Operative Gynäkologie

Hildesheim, North Rhine-Westphalia, Germany

Zentrum für ambulante gynäkologisch Onkologie (ZAGO)

Krefeld, North Rhine-Westphalia, Germany

Städtisches Klinikum Lüneburg Frauenklinik

Lüneburg, North Rhine-Westphalia, Germany

Johannes Wesling Klinikum Minden Innere Medizin, Hämatologie, Onkologie

Minden, North Rhine-Westphalia, Germany

Brustzentrum Niederrhein, im ev. Krankenhaus Bethesda

Mönchengladbach, North Rhine-Westphalia, Germany

Universitätsklinikum Münster AöR Brustzentrum

Münster, North Rhine-Westphalia, Germany

Marien Krankenhaus Schwerte MKS St. Paulus GmbH

Schwerte, North Rhine-Westphalia, Germany

Praxisnetz Hämatologie / internistische Onkologie

Troisdorf, North Rhine-Westphalia, Germany

Christliches Klinikum Unna Mitte Gynäkologie und Geburtshilfe

Unna, North Rhine-Westphalia, Germany

Marien Hospital Witten Brustzentrum

Witten, North Rhine-Westphalia, Germany

Helios Universitätsklinikum Wuppertal Landesfrauenklinik

Wuppertal, North Rhine-Westphalia, Germany

Praxisklinik für Hämatologie und Onkologie Koblenz

Koblenz, Rhineland-Palatinate, Germany

Klinikum Mutterhaus der Borromäerinnen Innere Medizin 1

Trier, Rhineland-Palatinate, Germany

Universitätsklinikum des Saarlandes Klinik für Frauenheilkunde

Homburg (Saar), Saarland, Germany

Caritas Traegergesellschaft Saarbruecken mbH (CTS) Frauenklinik

Saarbrücken, Saarland, Germany

Klinikum Chemnitz Frauenheilkunde und Geburtshilfe

Chemnitz, Saxony, Germany

Onkozentrum Dresden/Freiberg/Meißen

Dresden, Saxony, Germany

Gemeinschaftspraxis Dr. med. Johannes Mohm, Dr. med. Virág Siklaky, Stefanie Mann Onkopraxis Dresden

Dresden, Saxony, Germany

Universitätsklinikum Leipzig, Klinik und Poliklinik für Frauenheilkunde

Leipzig, Saxony, Germany

Klinikum St. Georg Gynäkologie und Geburtshilfe

Leipzig, Saxony, Germany

Klinikum Obergöltzsch Brustzentrum Vogtland

Rodewisch, Saxony, Germany

Universitätsklinikum Halle (UKH), Universitätsklinik und Poliklinik für Gynäkologie

Halle, Saxony-Anhalt, Germany

Klinikum Magdeburg Frauenheilkunde und Geburtshilfe

Magdeburg, Saxony-Anhalt, Germany

Johanniter Krankenhaus Frauenklinik

Stendal, Saxony-Anhalt, Germany

MediOnko-Institut GbR Praxiskliik Krebsheilkunde für Frauen/Brustzentrum

Berlin, , Germany

Praxis für gynäkologische Onkologie im Brustzentrum City am Sankt Gertrauden KH

Berlin, , Germany

HELIOS Klinikum Berlin-Buch GmbH

Berlin, , Germany

Onkologisch-Hämatologische Schwerpunktpraxis

Bremen, , Germany

AGAPLESION Diakonie-Klinikum Hamburg Gyn. Studienambulanz

Hamburg, , Germany

Mammazentrum Hamburg MVZ GbR

Hamburg, , Germany

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Uniwersytet Jagiellonski Collegium Medicum Szpital Uniwersytecki w Krakowie - Klinika Onkologii

Krakow, , Poland

MSCM Cancer Center and Institute of Oncology Department of Breast Cancer and Reconstructive Surgery

Warsaw, , Poland

Hospital Universitari Son Espases

Palma, Mallorca, Spain

Hospital Vall Hebron - Vall Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

Hospital Universitario San Pedro De Alcantara

Cáceres, , Spain

Hospital Universitario de Vinalopo

Elche, , Spain

Hospital Beata Maria Ana

Madrid, , Spain

Althaia Xarxa Assistencia

Manresa, , Spain

Hospital Regional Universitario Malaga

Málaga, , Spain

Hospital Universitario De Navarra

Pamplona, , Spain

Hospital Universitario San Juan De Alicante

Sant Joan d'Alacant, , Spain

Complejo Hospitalario Universitario Santiago de Compostela

Santiago de Compostela, , Spain

Hospital Quironsalud Sagrado Corazon

Seville, , Spain

Consorcio Hospital General Universitario De Valencia

Valencia, , Spain

Countries

Germany; Poland; Spain

Other Identifiers

2019-001488-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WSG-AM11 (ADAPTlate)

Identifier Type: -

Identifier Source: org_study_id