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JOURNAL ONKOLOGIE – STUDIE
ADAPTlate

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

Rekrutierend

NCT-Nummer:
NCT04565054

Studienbeginn:
September 2020

Letztes Update:
01.03.2024

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

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
West German Study Group

Collaborator:
Eli Lilly and Company, Genomic Health®, Inc.,

Studienleiter

Oleg Gluz, PD Dr. med.
Principal Investigator
Westdeutsche Studiengruppe GmbH

Kontakt

Studienlocations
(3 von 67)

Praxis für interdisziplinäre Onkologie & Hämatologie
79110 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Matthias Zaiss, Dr. med.

Norbert Marschner, Dr. med.» Ansprechpartner anzeigen
Studienzentrum Onkologie Ravensburg Prof. Dr. Dechow, Prof. Dr. Decker, Dr. Nonnenbroich GbR
88212 Ravensburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Thomas Decker, Prof. Dr.

Tobias Dechow, Prof. Dr.» Ansprechpartner anzeigen
Universitätsklinikum Tübingen Department für Frauengesundheit, Brustzentrum
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Andreas Hartkopf, Prof.Dr.

Tobias Engler, Dr.» Ansprechpartner anzeigen
Medizinisches Zentrum für Hämatologie und Onkologie München MVZ GmbH
80639 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christoph Salat, Prof. Dr.

Oliver Stoetzer, PD. Dr.» Ansprechpartner anzeigen
Hämatologisch-Onkologische Schwerpunktpraxis Würzburg GbR Dr. Schöttker/ Dr. Pretscher
97080 Würzburg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Dominik Pretscher, Dr. med.

Björn Schöttker, Dr. med.» Ansprechpartner anzeigen
Klinikum der Universität München Campus Großhadern Frauenheilunde und Geburtsklinik
81377 Muenchen
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Nadia Harbeck, Prof. Dr.

Rachel Würstlein» Ansprechpartner anzeigen
St. Josefs-Hospital Wiesbaden GmbH Ambulanz der Frauenklinik, Brustzentrum
65189 Wiesbaden
(Hessen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Antje Lehnert, Dr

Anna-Kathrin Bicker, Dr» Ansprechpartner anzeigen
Studien GbR Braunschweig Dr. Lorenz/Dr. Kreiss-Sender
38100 Braunschweig
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Janine Kreiss-Sender, Dr. med.

Ralf Lorenz, Dr. med.» Ansprechpartner anzeigen
MVZ II der Niels Stensen Kliniken Onkologie u. Hämatologie
49124 Georgsmarienhütte
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Kerstin Lüdtke-Heckenkamp, Dr. med.

Jost Christoph Wamhoff, Dr. med.» Ansprechpartner anzeigen
Kliniken der Stadt Köln Krankenhaus Köln-Holweide Medizinische Klinik Brustzentrum
51067 Köln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Mathias Warm, MD
Phone (ext.): 6707

Myriam Vincent» Ansprechpartner anzeigen
Marienhospital GmbH Studienzentrale Brustcentrum Aachen-Kreis Heinsberg
52066 Aachen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Mahmoud Danaei, Dr

Miriam Kohlschein» Ansprechpartner anzeigen
Evangelisches Krankenhaus Bergisch Gladbach gGmbH Brustzentrum,
51465 Bergisch Gladbach
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christian Rudlowski, Prof.Dr.

Lena Leitzen» Ansprechpartner anzeigen
Gynäkologisches Zentrum Bonn PD Dr. med. Christian Kurbacher
53111 Bonn
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christian Martin Kurbacher, PD. Dr.

Jutta Kurbacher» Ansprechpartner anzeigen
GYNONOVA GbR Schwerpunktpraxis für gynäkologische Onkologie
50679 Cologne
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Katja Ziegler-Löhr, Dr. med.

Solvejg Rellecke, Dr. med.» Ansprechpartner anzeigen
Universitätsklinikum Düsseldorf Frauenheilkunde und Geburtshilfe
40225 Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Tanja Fehm, Prof. Dr.

Eugen Ruckhäberle, Prof. Dr.» Ansprechpartner anzeigen
Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum
45136 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Mattea Reinisch, Dr. med.

Sherko Kümmel, Prof. Dr.» Ansprechpartner anzeigen
Universitätsklinikum Essen Frauenheilkunde und Geburtshilfe
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Oliver Hoffmann, PD. Dr.

Ann-Kathrin Bittner, PD. Dr.» Ansprechpartner anzeigen
Praxisgemeinschaft Gynäkologische Onkologie & Spezielle Operative Gynäkologie
31134 Hildesheim
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christoph Uleer, Dr. med.

Jasmin Pourfard, Dr. med.» Ansprechpartner anzeigen
Zentrum für ambulante gynäkologisch Onkologie - ZAGO Haus 03
47805 Krefeld
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Gunther Rogmans, Dr. med.

Marina Wirtz, Dr. med.» Ansprechpartner anzeigen
Johannes Wesling Klinikum Minden Innere Medizin, Hämatologie, Onkologie
32429 Minden
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Martin Griesshammer, Prof. Dr.

Hans-Joachim Tischler, Dr. med.» Ansprechpartner anzeigen
Brustzentrum Niederrhein, im ev. Krankenhaus Bethesda
41061 Moenchengladbach
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Oleg Gluz, PD. Dr. med.

Raquel von Schumann» Ansprechpartner anzeigen
Christliches Klinikum Unna Mitte Gynäkologie und Geburtshilfe
59423 Unna
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Cristin Kühn, Dr. med.

Heidi Wortelmann, Dr. med.» Ansprechpartner anzeigen
Universitätsklinikum des Saarlandes Klinik für Frauenheilkunde
66421 Homburg (Saar)
(Saarland)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Erich-Franz Solomayer, Prof. Dr.

Lisa Stotz, Dr. med.» Ansprechpartner anzeigen
Universitätsklinikum Halle (UKH), Universitätsklinik und Poliklinik für Gynäkologie
06120 Halle (Saale)
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christoph Thomssen, Prof. Dr.

Susanne Barrot, Dr. med.» Ansprechpartner anzeigen
Praxis für gynäkologische Onkologie im Brustzentrum City am Sankt Gertrauden KH
10713 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Lidia Perlova-Griff

Gerd Graffunder, Dr.» Ansprechpartner anzeigen
AGAPLESION Diakonie-Klinikum Hamburg Gyn. Studienambulanz
20259 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Mustafa Celalettin Ugur, Dr. med.

Theresa Bernard, Dr. med.» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. 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 outcome:

1. overall survival (OS) (Time Frame - at end of study, 3-6 years after start of treatment):
assessment of overall survival (OS) and distant DFS (dDFS) in both arms

2. differences in overall survival (OS) and dDFS (Time Frame - at end of study, 3-6 years after start of study treatment):
differences in overall survival (OS) and dDFS between arms

3. subgroup and multivariable survival analyses (Time Frame - at end of study, 3-6 years after start of study treatment):
subgroup and multivariable survival analyses

4. CNS metastases (Time Frame - at end of study, 3-6 years after start of study treatment):
occurrence of CNS metastases

5. EORTC QLQ-C30 (Time Frame - at end of study, on average 3-6 years after start of treatment):
quality of life (QoL)

6. EORTC QLQ-BR23 (Time Frame - at end of study, on average 3-6 years after start of treatment):
quality of life (QoL)

7. EQ-5D-5L (Time Frame - at end of study, on average 3-6 years after start of treatment):
quality of life (QoL)

Studien-Arme

  • 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
  • No Intervention: 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

Geprüfte Regime

  • Abemaciclib 50 MG; 150mg 1-0-1 per os (Verzenios):
    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

Quelle: ClinicalTrials.gov


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

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