Adj. Marker-adjusted Personalized Therapy Comparing ET+Ribociclib vs Chemotherapy in Intermediate Risk, HR+/HER2- EBC
NCT ID: NCT04055493
Last Updated: 2025-08-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
1684 participants
INTERVENTIONAL
2019-07-02
2027-07-31
Brief Summary
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Detailed Description
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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 very positive national and international feedback to the ADAPT concept as a whole.
The aim of this ADAPTcycle phase-III-trial is to investigate whether the intermediate-risk patient group identified during the screening phase derives additional benefit from treatment with ribociclib in combination with ET compared to chemotherapy (followed by adjuvant ET).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Ribociclib plus ET
Ribociclib 600mg / day over 26 cycles + endocrine treatment of physician´s choice
Ribociclib 200Mg Oral Tablet
3 x 200 MG per os
Standard-of-care chemotherapy
Standard-of-care chemotherapy according to the clinical guidelines, e.g., of the Breast Committee of the German Gynecological Oncology Group (AGO), and regional prescribing information depending on patient's needs for 16-24 weeks,
No interventions assigned to this group
Interventions
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Ribociclib 200Mg Oral Tablet
3 x 200 MG per os
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
A. Prior to REGISTRATION in the study:
1\. Written informed consent prior to any screening procedures. 2. Female. 3. ≥ 18 years of age. 4a. EITHER: (Post)menopausal status at the time of initiation of (neo)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, toremifene, or ovarian suppression) and/or FSH and estradiol in the postmenopausal range per local normal range.
4b. OR: Pre-menopausal patients:
* confirmed negative serum pregnancy test (β-hCG) before starting study treatment, or
* patient has had a hysterectomy. 5. Histologically confirmed diagnosis of primary estrogen-receptor positive and/or progesterone-receptor positive (\> 1%) early breast cancer by local laboratory.
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 most recently analyzed tissue sample and all tested by a local laboratory).
7\. Local therapy of breast cancer (if adjuvant treatment or planned if neoadjuvant treatment) according to current guidelines.
Note: This may include radiotherapy of breast cancer.
B. Prior to RANDOMIZATION in the study 8. No evidence of distant metastasis (confirmed prior to randomization by, preferentially, CT thorax / abdomen, X-ray chest, ultrasound liver, bone scan, or PET-CT).
9\. Patient has available tumor tissue from diagnostic biopsy. 10. Patient is classified as intermediate risk according to the ADAPT intermediate-risk definition (i) (as follows), or (only in case of missing Oncotype DX or Ki-67 response data), according to the clinical intermediate-risk definition (ii) (as follows).
(i). ADAPT intermediate-risk definition: Patient meets one of the following criteria:
* c/pN0, RS ≤ 25 with luminal-B-like (Ki-67 ≥20% or G3) or c/pT2-4 without endocrine response (post-endocrine Ki-67 \> 10 %)
* c/pN1, RS ≤ 25 without endocrine response (post-endocrine Ki-67 \> 10 %)
* c/pN0, RS \> 25 with luminal-B-like (Ki-67 ≥20% or G3) or c/pT2-4 with endocrine response (Ki-67 ≤ 10 %)
* c/pN1, RS \> 25 with endocrine response (Ki-67 ≤ 10 %)
* c/pN2-3, RS ≤ 25 with endocrine response (Ki-67 ≤ 10 %). Note: Postmenopausal patients with pT1-2/pN0 disease and RS \< 25, as well as premenopausal patients with pT1-2/pN0 disease and RS\<16, are recommended to be treated by endocrine therapy alone and not to be randomized (at investigator´s discretion).
(ii). Clinical intermediate-risk definition (ascertained by investigator): Clinical intermediate risk may be ascertained by the investigator prior to randomization if at maximum two of the following three risk factors are present (according to primary diagnosis / 1st sample):
1. cT2-4
2. c/pN positive
3. G3 and / or Ki-67 ≥ 20% Note: Inclusion of a patient according to "clinical intermediate risk" is permitted only in case of missing baseline Oncotype DX® or Ki-67 decrease. In this case, investigators will follow a risk-based, step-wise assessment process.
11\. No contraindication for (neo)-adjuvant ET. 12. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 13. 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 ≥ 9.0 g/dL,
* estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by a Cockcroft-Gault formula,
* INR ≤ 1.5,
* serum creatinine \< 1.5 mg/dL,
* total bilirubin \< ULN, except for patients with Gilbert's Syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN,
* aspartate transaminase (AST) \< 2.5 × ULN,
* alanine transaminase (ALT) \< 2.5 × ULN. 14. 2-lead-ECG (CANKADO) with:
* QTcF interval at screening \< 450 msec (using Fridericia's correction),
* mean resting heart rate 50-90 bpm (determined from the ECG). 15. Ability to swallow ribociclib tablets or to administer other study medication, respectively.
16\. Ability to communicate with the investigator and comply with study procedures.
17\. Willing to remain during therapy at the clinical site, as required by the protocol.
Exclusion Criteria
1. Patient with distant metastases of breast cancer beyond regional lymph nodes.
2. Patient has received prior (neo)-adjuvant treatment with chemotherapy, ET, or any CDK4/6 inhibitor for breast cancer.
3. Patient has received tamoxifen, raloxifene, or aromatase inhibitors (AIs) for reduction in risk ("chemoprevention") of breast cancer and/or treatment for osteoporosis within last 2 years prior to screening.
4. Patient has received prior neoadjuvant/adjuvant treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin or 900 mg/m² or more for epirubicin.
5. Patient with a known hypersensitivity to any of the excipients of ribociclib, ET, or standard-of-care chemotherapy.
6. Patient with inflammatory breast cancer at screening.
7. Patient is concurrently using other anti-cancer therapy.
8. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
9. Patient is currently receiving warfarin or other coumarin-derived anti-coagulant for treatment, prophylaxis, or otherwise.
10. Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 5.0 Grade ≤ 1.
11. Patient has a concurrent malignancy, or malignancy within 5 years of randomization, or known history of invasive breast cancer.
12. 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).
13. Patient has a known history of HIV infection.
14. Patient has known active hepatitis-B-virus (HBV) or hepatitis-C-virus (HCV) infection.
15. 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., chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial, or viral infections, etc.).
16. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
* history of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry,
* documented cardiomyopathy,
* left ventricular ejection fraction (LVEF) \< 50 % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO),
* long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome, or any of the following:
* risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/ symptomatic bradycardia,
* concomitant medications with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g., within 5 half-lives or 7 days prior to starting study drug),
* inability to determine the QTcF interval,
* clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left-bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II, and 3rd-degree AV block),
* systolic blood pressure (SBP) \> 160 or \< 90 mmHg.
17. Patient is currently receiving any of the following substances, which cannot be discontinued 7 days prior to Cycle 1 Day 1:
* concomitant medications, herbal supplements, fruits (e.g. grapefruit, pomegranates, pomelos, star fruit, Seville oranges) and their juices that are strong inducers or inhibitors of CYP3A4/5,
* medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
18. Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
19. Participation in a prior investigational study within 30 days prior to enrollment or within five half-lives of the investigational product, whichever is longer.
20. Not able to understand and to comply with study instructions and requirements.
21. Pregnant or nursing (lactating) woman.
22. 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:
* total abstinence (when this is in line with the preferred and usual lifestyle of the patient).
* female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment.
* 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.
* placement of an intrauterine device (IUD).
23. Use of oral (estrogen and progesterone), transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy.
18 Years
FEMALE
No
Sponsors
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Novartis
INDUSTRY
Genomic Health®, Inc.
INDUSTRY
West German Study Group
OTHER
Responsible Party
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Principal Investigators
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Nadia Harbeck, Prof. Dr.
Role: PRINCIPAL_INVESTIGATOR
Ludwigs-Maximilians-University Munich, Breast Cancer Centre
Locations
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Ost-Alb Klinikum Brustzentrum
Aalen, Baden-Wurttemberg, Germany
Stadtklinik Baden-Baden Brustzentrum
Baden-Baden, Baden-Wurttemberg, Germany
Kreiskliniken Böblingen Klinikum Böblingen Frauenklinik
Böblingen, Baden-Wurttemberg, Germany
Uniklinikum Freiburg Frauenklinik
Freiburg im Breisgau, Baden-Wurttemberg, Germany
Praxis für interdisziplinäre Onkologie & Hämatologie GbR Praxis am Diakonieklinikum
Freiburg im Breisgau, Baden-Wurttemberg, Germany
SLK-Kliniken-Heilbronn Frauenklinik
Heilbronn, Baden-Wurttemberg, Germany
Klinikum Ludwigsburg Klinik für Frauenheilkunde u. Geburtshilfe
Ludwigsburg, Baden-Wurttemberg, Germany
Universitätsklinikum Tübingen Universitäts-Frauenklinik
Tübingen, Baden-Wurttemberg, Germany
Universitätsfrauenklinik Ulm Frauenheilkunde und Geburtshilfe
Ulm, Baden-Wurttemberg, Germany
GRN Klinik Weinheim Gynäkologie
Weinheim, Baden-Wurttemberg, Germany
Klinikum der Universität München Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Brustzentrum
Munich, Bavaria, Germany
Rotkreuzkliniken München Frauenklinik - Gynäkologie
München, Bavaria, Germany
Frauenklinik und Poliklinik / Studienzentrale Josef-Schneider-Straße 4
Würzburg, Bavaria, Germany
Carl-Thiem-Klinikum / Brustzentrum Senologie der Frauenklinik
Cottbus, Brandenburg, Germany
Schwerpunktpraxis Gynäkologische Onkologie Praxis Dr. Heinrich
Fürstenwalde, Brandenburg, Germany
Klinikum Ernst von Bergmann Klinik für Gynäkologie und Geburtshilfe
Potsdam, Brandenburg, Germany
Klinikum Bremerhaven Reinkenheide Frauenklinik
Bremerhaven, City state Bremen, Germany
AGAPLESION Markus Krankenhaus / Brustzentrum Gynäkologie und Geburtshilfe
Frankfurt am Main, Hesse, Germany
Klinikum Frankfurt Höchst Klinik für Gynäkologie und Geburtshilfe
Frankfurt am Main, Hesse, Germany
Klinikum Kassel Frauenklinik
Kassel, Hesse, Germany
Sana Klinikum Klinik für Gynäkologie und Geburtshilfe, Studienambulanz AOZ
Offenbach, Hesse, Germany
St. Josefs-Hospital Wiesbaden Frauenklinik - Gynäkologie
Wiesbaden, Hesse, Germany
Frauenärzte Casparistraße Studien GbR BS
Braunschweig, Lower Saxony, Germany
MVZ II der Niels Stensen Kliniken Onkologie u. Hämatologie, Brustzenzrum
Georgsmarienhütte, Lower Saxony, Germany
Medizinische Hochschulle Hannover Klinik für Frauenheilkunde und Geburtshilfe
Hanover, Lower Saxony, Germany
DIAKOVERE Henriettenstift Frauenklinik
Hanover, Lower Saxony, Germany
Gynäkologische Gemeinschaftspraxis-Ärztehaus am Bahnhofsplatz Klinische Studien
Hildesheim, Lower Saxony, Germany
Städtisches Klinikum Lüneburg Frauenklinik
Lüneburg, Lower Saxony, Germany
MVZ Klinik Dr. Hancken Haematologie/Onkologie
Stade, Lower Saxony, Germany
UFK Klinikum Südstadt Frauenklinik
Rostock, Mecklenburg-Vorpommern, Germany
Marienhospital Studienzentrale BrustCentrum Aachen-Kreis Heinsberg
Aachen, North Rhine-Westphalia, Germany
Universitätsklinikum Aachen, Frauenklinik - Senologie
Aachen, North Rhine-Westphalia, Germany
EVK Bergisch Gladbach Brustzentrum
Bergisch Gladbach, North Rhine-Westphalia, Germany
Onkologische Schwerpunktpraxis Bielefeld Praxis Dr. Just
Bielefeld, North Rhine-Westphalia, Germany
Marienhospital Bottrop Klinik für Gynäkologie und Geburtshilfe / Gyn-Ambulanz
Bottrop, North Rhine-Westphalia, Germany
St. Elisabeth-Krankenhaus Hohenlind Brustzentrum
Cologne, North Rhine-Westphalia, Germany
Uniklinik Köln / Gebäude 70 Studienzentrale der Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
Cologne, North Rhine-Westphalia, Germany
Kliniken der Stadt Köln / Krankenhaus Holweide Brustzentrum Holweide
Cologne, North Rhine-Westphalia, Germany
Klinikum Dortmund gGmbH Frauenklinik
Dortmund, North Rhine-Westphalia, Germany
Universitätsklinikum Düsseldorf Klinik für Frauenheilkunde & Geburtshilfe
Düsseldorf, North Rhine-Westphalia, Germany
Luisenkrankenhaus GmbH GynOnco Düsseldorf
Düsseldorf, North Rhine-Westphalia, Germany
Praxis Dr. Adhami
Erkelenz, North Rhine-Westphalia, Germany
St. Antonius Hospital Klinik für Hämatologie/Onkologie
Eschweiler, North Rhine-Westphalia, Germany
Universitätsklinikum Essen Klinik für Frauenheilkunde und Geburtshilfe
Essen, North Rhine-Westphalia, Germany
Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum
Essen, North Rhine-Westphalia, Germany
Evangelische Kliniken Gelsenkirchen GmbH Klinik für Senologie
Gelsenkirchen, North Rhine-Westphalia, Germany
Wilhelm-Anton-Hospital Goch Klinik für Innere Medizin, Hämatologie u. Onkologie
Goch, North Rhine-Westphalia, Germany
Onkodok GmbH
Gütersloh, North Rhine-Westphalia, Germany
St. Barbara Klinik Brustzentrum
Hamm, North Rhine-Westphalia, Germany
Klinikum Leverkusen Medizinische Klinik 3
Leverkusen, North Rhine-Westphalia, Germany
Praxis für gynäkologische Onkologie am Ev. Krankenhaus Bethesda
Mönchengladbach, North Rhine-Westphalia, Germany
St. Franziskus-Hospital Brustzentrum
Münster, North Rhine-Westphalia, Germany
Universitätsklinikum Frauenheilkunde
Münster, North Rhine-Westphalia, Germany
ONCOLOGIANOVA Praxis Dr. Emde
Recklinghausen, North Rhine-Westphalia, Germany
Marienkrankenhaus Schwerte Brustzentrum
Schwerte, North Rhine-Westphalia, Germany
Marien-Krankenhaus Klinik für Gynäkologie und Geburtshilfe
Siegen, North Rhine-Westphalia, Germany
Diakonie Klinikum Jung Stilling Brustzentrum
Siegen, North Rhine-Westphalia, Germany
Praxisnetz Hämatologie / internistische Onkologie Praxis Troisdorf
Troisdorf, North Rhine-Westphalia, Germany
Christliches Klinikum Unna gGmbH Brustzentrum
Unna, North Rhine-Westphalia, Germany
Praxis für Hämatologie und internistische Onkologie Praxis Dr. Nusch
Velbert, North Rhine-Westphalia, Germany
Marien Hospital / Senologie Brustzentrum
Witten, North Rhine-Westphalia, Germany
Helios Universitätsklinikum Frauenheilkunde & Geburtshilfe
Wuppertal, North Rhine-Westphalia, Germany
Katholisches Klinikum Koblenz-Montabaur-Marienhof Koblenz Marienhof Koblenz - Gynäkologie
Koblenz, Rhineland-Palatinate, Germany
Klinikum Mutterhaus der Borromäerinnen Innere Medizin I / Onkologie
Trier, Rhineland-Palatinate, Germany
Universitätsklinikum des Saarlandes Frauenklinik
Homburg, Saarland, Germany
DRK Kliniken Saar / Krankenhaus Saarlouis Brustzentrum
Saarlouis, Saarland, Germany
Klinikum Chemnitz Frauenklinik / Brustzentrum
Chemnitz, Saxony, Germany
Universitätsklinikum Dresden Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
Dresden, Saxony, Germany
Universitätsklinikum Leipzig Gynäkologie und Universitäres Krebszentrum; Klinik und Poliklinik für Frauenheilkunde
Leipzig, Saxony, Germany
Kliniken St. Georg Klinik für Gynäkologie und Geburtshilfe
Leipzig, Saxony, Germany
Klinikum Obergöltzsch-Rodewisch Frauenklinik
Rodewisch, Saxony, Germany
Universitätsklinikum Halle Universitätsklinik für Gynäkologie
Halle, Saxony-Anhalt, Germany
Altmark-Klinikum Salzwedel Klinik für Frauenheilkunde
Salzwedel, Saxony-Anhalt, Germany
Johanniter Frauenklinik Stendal Gynäkologie
Stendal, Saxony-Anhalt, Germany
Universitätsklinikum Schleswig-Holstein Campus Lübeck, Frauenklinik
Lübeck, Schleswig-Holstein, Germany
Universitätsklinikum Jena Klinik und Poliklinik für Frauenheilkunde und Fortpflanzungsmedizin
Jena, Thuringia, Germany
MVZ Nordhausen Praxis Dr. Andrea Grafe
Nordhausen, Thuringia, Germany
Charité Berlin, Klinik für Gynäkologie m.S. Senologie Brustzentrum (CCM)
Berlin, , Germany
St. Gertrauden Krankenhaus Brustzentrum City Berlin
Berlin, , Germany
Vivantes Klinikum Am Urban Brustzentrum
Berlin, , Germany
DRK Klinikum Berlin-Köpenick Brustzentrum
Berlin, , Germany
Evangelisches Waldkrankenhaus Spandau Klinik für Gynäkologie und Geburtshilfe
Berlin, , Germany
Hämatologisch/Onkologische Schwerpunktpraxis Praxis Dr. Schreiber
Bremen, , Germany
UKE Hamburg / Frauenklinik Brustzentrum am UKE
Hamburg, , Germany
Agaplesion Diakonieklinikum Hamburg Frauenklinik, Brustzentrum u. Gyn. Tumorzentrum / Gyn. Studienambulanz
Hamburg, , Germany
Mammazentrum Hamburg am Krankenhaus Jerusalem
Hamburg, , Germany
Countries
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References
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Klier K, Patel YJ, Schinkothe T, Harbeck N, Schmidt A. Corrected QT Interval (QTc) Diagnostic App for the Oncological Routine: Development Study. JMIR Cardio. 2023 Sep 11;7:e48096. doi: 10.2196/48096.
Other Identifiers
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WSG-AM08 (ADAPTcycle)
Identifier Type: -
Identifier Source: org_study_id
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