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

Breast Cancer Female Clinical Trial

— ADAPTlate  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04565054
• Other study ID #: WSG-AM11
• Secondary ID: 2019-001488-60
• Status: Recruiting
• Phase: Phase 3
• Start date: September 2, 2020
• Est. completion date: March 2028

Study information

• Verified date: February 2024
• Source: West German Study Group
• Contact: Anja Braschoß, MD
• Phone: +4917682119153
• Email: anja.braschoss[@]wsg-online.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1260
• Est. completion date: March 2028
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 (ß-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.

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Germany	Marienhospital GmbH Studienzentrale Brustcentrum Aachen-Kreis Heinsberg	Aachen	NRW
Germany	Uniklinik RWTH Aachen Gynäkologie und Geburtsmedizin	Aachen	NRW
Germany	Gemeinschaftspraxis Dr. Heinrich, Prof. Dr. Bangerter	Augsburg	Bavaria
Germany	Evangelisches Krankenhaus Bergisch Gladbach gGmbH Brustzentrum,	Bergisch Gladbach	NRW
Germany	DRK Kliniken Berlin Köpenick Brustzentrum im Onkozentrum	Berlin
Germany	MediOnko-Institut GbR	Berlin
Germany	Praxis für gynäkologische Onkologie im Brustzentrum City am Sankt Gertrauden KH	Berlin
Germany	Onkologische Schwerpunktpraxis Bielefeld	Bielefeld	NRW
Germany	Gynäkologisches Zentrum Bonn PD Dr. med. Christian Kurbacher	Bonn	NRW
Germany	Studien GbR Braunschweig Dr. Lorenz/Dr. Kreiss-Sender	Braunschweig	Lower Saxony
Germany	Onkologisch-Hämatologische Schwerpunktpraxis	Bremen
Germany	Klinikum Chemnitz Frauenheilkunde und Geburtshilfe	Chemnitz	Saxony
Germany	GYNONOVA GbR Schwerpunktpraxis für gynäkologische Onkologie	Cologne	NRW
Germany	Carl-Thiem-Klinikum Cottbus Frauenklinik	Cottbus	Brandenburg
Germany	Onkologische Gemeinschaftspraxis	Dresden	Saxony
Germany	Onkozentrum Dresden/Freiberg	Dresden	Saxony
Germany	Luisenkrankenhaus Brustzentrum	Düsseldorf	NRW
Germany	Universitätsklinikum Düsseldorf Frauenheilkunde und Geburtshilfe	Düsseldorf	NRW
Germany	St.-Antonius-Hospital Eschweiler Hämatologie/Onkologie	Eschweiler	NRW
Germany	Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum	Essen	NRW
Germany	Universitätsklinikum Essen Frauenheilkunde und Geburtshilfe	Essen	NRW
Germany	Onco Medical Consult GmbH	Frankfurt a.M.	Hesse
Germany	Praxis für interdisziplinäre Onkologie & Hämatologie	Freiburg	Baden-Württemberg
Germany	MVZ II der Niels Stensen Kliniken Onkologie u. Hämatologie	Georgsmarienhütte	Niedersachsen
Germany	ÜBAG MVZ Onkologische Kooperation Harz	Goslar	Lower Saxony
Germany	Onkologische Schwerpunktpraxis	Gütersloh	NRW
Germany	Universitätsklinikum Halle (UKH), Universitätsklinik und Poliklinik für Gynäkologie	Halle (Saale)	Saxony Anhalt
Germany	AGAPLESION Diakonie-Klinikum Hamburg Gyn. Studienambulanz	Hamburg
Germany	Mammazentrum Hamburg MVZ GbR	Hamburg
Germany	Diakovere Henriettenstift Frauenklinik	Hannover	Niedersachsen
Germany	Medizinische Hochschule Hannover Frauenheilkunde	Hannover	Lower Saxony
Germany	SLK Kliniken Heilbronn Klinik für Gynäkologie und Geburtshilfe	Heilbronn	Baden-Württemberg
Germany	Praxisgemeinschaft Gynäkologische Onkologie & Spezielle Operative Gynäkologie	Hildesheim	NRW
Germany	Universitätsklinikum des Saarlandes Klinik für Frauenheilkunde	Homburg (Saar)	Saarland
Germany	Brustzentrum, Elisabeth-Krankenhaus gGmbH	Kassel
Germany	Praxisklinik für Hämatologie und Onkologie Koblenz	Koblenz	Rhineland-Palatinate
Germany	Kliniken der Stadt Köln Krankenhaus Köln-Holweide Medizinische Klinik Brustzentrum	Köln	Nordrhein-Westfalen
Germany	St. Elisabeth-Krankenhaus GmbH, Brustzentrum - Senologie	Köln	NRW
Germany	Zentrum für ambulante gynäkologisch Onkologie - ZAGO Haus 03	Krefeld	NRW
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie	Langen	Hesse
Germany	Onkologie UnterEms Leer-Emden-Papenburg Dr. L. Müller	Leer	Lower Saxony
Germany	Klinikum St. Georg Gynäkologie und Geburtshilfe	Leipzig	Saxony
Germany	Städtisches Klinikum Lüneburg Frauenklinik	Lüneburg	NRW
Germany	Klinikum Magdeburg Frauenheilkunde und Geburtshilfe	Magdeburg	Saxony-Anhalt
Germany	Johannes Wesling Klinikum Minden Innere Medizin, Hämatologie, Onkologie	Minden	NRW
Germany	Brustzentrum Niederrhein, im ev. Krankenhaus Bethesda	Moenchengladbach	NRW
Germany	Klinikum der Universität München Campus Großhadern Frauenheilunde und Geburtsklinik	Muenchen	Bayern
Germany	Rotkreuzkliniken München, Interdisziplinbäres Brustzentrum	München	Bayern
Germany	Medizinisches Zentrum für Hämatologie und Onkologie München MVZ GmbH	Munich	Bavaria
Germany	Universitätsklinikum Münster Brustzentrum	Münster	NRW
Germany	Pius-Hospital Oldenburg Hämatologie, Onkologie	Oldenburg	Lower Saxony
Germany	Klinikum Ernst von Bergmann gGmbH Brustzentrum	Potsdam	Brandenburg
Germany	Studienzentrum Onkologie Ravensburg Prof. Dr. Dechow, Prof. Dr. Decker, Dr. Nonnenbroich GbR	Ravensburg	Baden-Württemberg
Germany	Klinikum Obergöltzsch Brustzentrum Vogtland	Rodewisch	Sachsen
Germany	Klinikum Südstadt Rostock Frauenklinik	Rostock	Mecklenburg-Vorpommern
Germany	Caritas Traegergesellschaft Saarbruecken mbH (CTS) Frauenklinik	Saarbrücken
Germany	Marien Krankenhaus Schwerte MKS St. Paulus GmbH	Schwerte	NRW
Germany	Johanniter Krankenhaus Frauenklinik	Stendal	Saxony-Anhalt
Germany	Klinikum Mutterhaus der Borromäerinnen Innere Medizin 1	Trier	Rheinland-Pfalz
Germany	Universitätsklinikum Tübingen Department für Frauengesundheit, Brustzentrum	Tübingen	Baden-Wüttenburg
Germany	Universitätsklinikum Ulm Frauenheilkunde, Geburtshilfe	Ulm	Baden-Württemberg
Germany	Christliches Klinikum Unna Mitte Gynäkologie und Geburtshilfe	Unna	NRW
Germany	GRN-Klinik Weinheim Gynäkologie und Geburtshilfe	Weinheim	Baden-Württemberg
Germany	St. Josefs-Hospital Wiesbaden GmbH Ambulanz der Frauenklinik, Brustzentrum	Wiesbaden	Hessen
Germany	Marien Hospital Witten Brustzentrum	Witten	NRW
Germany	Helios Klinikum Wuppertal Landesfrauenklinik	Wuppertal	NRW
Germany	Hämatologisch-Onkologische Schwerpunktpraxis Würzburg GbR Dr. Schöttker/ Dr. Pretscher	Würzburg	Bavaria

Sponsors (3)

Lead Sponsor	Collaborator
West German Study Group	Eli Lilly and Company, Genomic Health®, Inc.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	invasive disease-free survival (iDFS)	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.	at end of study, 3-6 years after start of study treatment
Secondary	overall survival (OS)	assessment of overall survival (OS) and distant DFS (dDFS) in both arms	at end of study, 3-6 years after start of treatment
Secondary	differences in overall survival (OS) and dDFS	differences in overall survival (OS) and dDFS between arms	at end of study, 3-6 years after start of study treatment
Secondary	subgroup and multivariable survival analyses	subgroup and multivariable survival analyses	at end of study, 3-6 years after start of study treatment
Secondary	CNS metastases	occurrence of CNS metastases	at end of study, 3-6 years after start of study treatment
Secondary	EORTC QLQ-C30	quality of life (QoL)	at end of study, on average 3-6 years after start of treatment
Secondary	EORTC QLQ-BR23	quality of life (QoL)	at end of study, on average 3-6 years after start of treatment
Secondary	EQ-5D-5L	quality of life (QoL)	at end of study, on average 3-6 years after start of treatment