Adj. Marker-adjusted Personalized Therapy Comparing ET+Ribociclib vs Chemotherapy in Intermediate Risk, HR+/HER2- EBC

NCT04055493 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: WSG-AM08 (ADAPTcycle)
• Study Type: interventional
• Target: 1,684
• Locations: 1 country
• Sites: 86

Brief Summary

The study investigates, whether the patient group with intermediate-risk early breast cancer benefits from treatment with ribociclib in combination with endocrine therapy compared to standard-of-care chemotherapy (followed by adjuvant endocrine therapy).

Conditions

Breast Cancer Female

Keywords

early breast cancer; ADAPT; endocrine therapy; ribociclib; intermediate risk; HER2 negative; HR positive

Outcome Measures

Primary Outcomes (2)

• invasive disease-free survival (iDFS)

  superiority in invasive disease-free survival (iDFS) of ribociclib + ET vs. standard-of-care chemotherapy

  at end of study, on average 5 years after start of treatment

• distant disease-free survival (dDFS)

  distant disease-free survival (dDFS) in the ribociclib + ET-group to demonstrate survival rate \>92%

  at end of study, on average 5 years after start of treatment

Secondary Outcomes (7)

• overall survival (OS) 95 % CI

  at end of study, on average 5 years after start of treatment

• distant disease-free survival (dDFS) 95 % CI

  at end of study, on average 5 years after start of treatment

• QoL

  at end of study, on average 5 years after start of treatment

• treatment adherence

  at end of study, on average 5 years after start of treatment

• pathological complete response (pCR)

  at end of study, on average 5 years after start of treatment

Study Arms (2)

Ribociclib plus ET

EXPERIMENTAL

Ribociclib 600mg / day over 26 cycles + endocrine treatment of physician´s choice

Drug: Ribociclib 200Mg Oral Tablet

Standard-of-care chemotherapy

NO INTERVENTION

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,

Interventions

Ribociclib 200Mg Oral Tablet DRUG

3 x 200 MG per os

Also known as: Kisqali

Ribociclib plus ET

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pre- and postmenopausal women 18 years or older.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Prior to REGISTRATION in the study:
• \. 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.
• b. 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.
• \. 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).
• \. 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).
• \. 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).

You may not qualify if:

• Patient with distant metastases of breast cancer beyond regional lymph nodes.
• Patient has received prior (neo)-adjuvant treatment with chemotherapy, ET, or any CDK4/6 inhibitor for breast cancer.
• 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.
• 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.
• Patient with a known hypersensitivity to any of the excipients of ribociclib, ET, or standard-of-care chemotherapy.
• Patient with inflammatory breast cancer at screening.
• Patient is concurrently using other anti-cancer therapy.
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
• Patient is currently receiving warfarin or other coumarin-derived anti-coagulant for treatment, prophylaxis, or otherwise.
• Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 5.0 Grade ≤ 1.
• Patient has a concurrent malignancy, or malignancy within 5 years of randomization, or known history of invasive breast cancer.
• 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 a known history of HIV infection.
• Patient has known active hepatitis-B-virus (HBV) or hepatitis-C-virus (HCV) infection.
• 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.).

Sponsors & Collaborators

• West German Study Group: lead
• Novartis: collaborator
• Genomic Health®, Inc.: collaborator

Study Sites (86)

Ost-Alb Klinikum Brustzentrum

Aalen, Baden-Wurttemberg, 73430, Germany

Location

Stadtklinik Baden-Baden Brustzentrum

Baden-Baden, Baden-Wurttemberg, 76532, Germany

Location

Kreiskliniken Böblingen Klinikum Böblingen Frauenklinik

Böblingen, Baden-Wurttemberg, 71032, Germany

Location

Uniklinikum Freiburg Frauenklinik

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Praxis für interdisziplinäre Onkologie & Hämatologie GbR Praxis am Diakonieklinikum

Freiburg im Breisgau, Baden-Wurttemberg, 79110, Germany

Location

SLK-Kliniken-Heilbronn Frauenklinik

Heilbronn, Baden-Wurttemberg, 74078, Germany

Location

Klinikum Ludwigsburg Klinik für Frauenheilkunde u. Geburtshilfe

Ludwigsburg, Baden-Wurttemberg, 71640, Germany

Location

Universitätsklinikum Tübingen Universitäts-Frauenklinik

Tübingen, Baden-Wurttemberg, 72016, Germany

Location

Universitätsfrauenklinik Ulm Frauenheilkunde und Geburtshilfe

Ulm, Baden-Wurttemberg, 89075, Germany

Location

GRN Klinik Weinheim Gynäkologie

Weinheim, Baden-Wurttemberg, 69469, Germany

Location

Klinikum der Universität München Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Brustzentrum

Munich, Bavaria, 80337, Germany

Location

Rotkreuzkliniken München Frauenklinik - Gynäkologie

München, Bavaria, 80637, Germany

Location

Frauenklinik und Poliklinik / Studienzentrale Josef-Schneider-Straße 4

Würzburg, Bavaria, 97080, Germany

Location

Carl-Thiem-Klinikum / Brustzentrum Senologie der Frauenklinik

Cottbus, Brandenburg, 03048, Germany

Location

Schwerpunktpraxis Gynäkologische Onkologie Praxis Dr. Heinrich

Fürstenwalde, Brandenburg, 15517, Germany

Location

Klinikum Ernst von Bergmann Klinik für Gynäkologie und Geburtshilfe

Potsdam, Brandenburg, 14467, Germany

Location

Klinikum Bremerhaven Reinkenheide Frauenklinik

Bremerhaven, City state Bremen, 27574, Germany

Location

AGAPLESION Markus Krankenhaus / Brustzentrum Gynäkologie und Geburtshilfe

Frankfurt am Main, Hesse, 60431, Germany

Location

Klinikum Frankfurt Höchst Klinik für Gynäkologie und Geburtshilfe

Frankfurt am Main, Hesse, 65929, Germany

Location

Klinikum Kassel Frauenklinik

Kassel, Hesse, 34125, Germany

Location

Sana Klinikum Klinik für Gynäkologie und Geburtshilfe, Studienambulanz AOZ

Offenbach, Hesse, 63069, Germany

Location

St. Josefs-Hospital Wiesbaden Frauenklinik - Gynäkologie

Wiesbaden, Hesse, 65189, Germany

Location

Frauenärzte Casparistraße Studien GbR BS

Braunschweig, Lower Saxony, 38100, Germany

Location

MVZ II der Niels Stensen Kliniken Onkologie u. Hämatologie, Brustzenzrum

Georgsmarienhütte, Lower Saxony, 49124, Germany

Location

Medizinische Hochschulle Hannover Klinik für Frauenheilkunde und Geburtshilfe

Hanover, Lower Saxony, 30539, Germany

Location

DIAKOVERE Henriettenstift Frauenklinik

Hanover, Lower Saxony, 30559, Germany

Location

Gynäkologische Gemeinschaftspraxis-Ärztehaus am Bahnhofsplatz Klinische Studien

Hildesheim, Lower Saxony, 31134, Germany

Location

Städtisches Klinikum Lüneburg Frauenklinik

Lüneburg, Lower Saxony, 21339, Germany

Location

MVZ Klinik Dr. Hancken Haematologie/Onkologie

Stade, Lower Saxony, 21680, Germany

Location

UFK Klinikum Südstadt Frauenklinik

Rostock, Mecklenburg-Vorpommern, 18059, Germany

Location

Marienhospital Studienzentrale BrustCentrum Aachen-Kreis Heinsberg

Aachen, North Rhine-Westphalia, 52066, Germany

Location

Universitätsklinikum Aachen, Frauenklinik - Senologie

Aachen, North Rhine-Westphalia, 52074, Germany

Location

EVK Bergisch Gladbach Brustzentrum

Bergisch Gladbach, North Rhine-Westphalia, 51465, Germany

Location

Onkologische Schwerpunktpraxis Bielefeld Praxis Dr. Just

Bielefeld, North Rhine-Westphalia, 33604, Germany

Location

Marienhospital Bottrop Klinik für Gynäkologie und Geburtshilfe / Gyn-Ambulanz

Bottrop, North Rhine-Westphalia, 46236, Germany

Location

St. Elisabeth-Krankenhaus Hohenlind Brustzentrum

Cologne, North Rhine-Westphalia, 50935, Germany

Location

Uniklinik Köln / Gebäude 70 Studienzentrale der Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Kliniken der Stadt Köln / Krankenhaus Holweide Brustzentrum Holweide

Cologne, North Rhine-Westphalia, 51067, Germany

Location

Klinikum Dortmund gGmbH Frauenklinik

Dortmund, North Rhine-Westphalia, 44137, Germany

Location

Universitätsklinikum Düsseldorf Klinik für Frauenheilkunde & Geburtshilfe

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Luisenkrankenhaus GmbH GynOnco Düsseldorf

Düsseldorf, North Rhine-Westphalia, 40235, Germany

Location

Praxis Dr. Adhami

Erkelenz, North Rhine-Westphalia, 41812, Germany

Location

St. Antonius Hospital Klinik für Hämatologie/Onkologie

Eschweiler, North Rhine-Westphalia, 52249, Germany

Location

Universitätsklinikum Essen Klinik für Frauenheilkunde und Geburtshilfe

Essen, North Rhine-Westphalia, 45130, Germany

Location

Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum

Essen, North Rhine-Westphalia, 45136, Germany

Location

Evangelische Kliniken Gelsenkirchen GmbH Klinik für Senologie

Gelsenkirchen, North Rhine-Westphalia, 45879, Germany

Location

Wilhelm-Anton-Hospital Goch Klinik für Innere Medizin, Hämatologie u. Onkologie

Goch, North Rhine-Westphalia, 47574, Germany

Location

Onkodok GmbH

Gütersloh, North Rhine-Westphalia, 33332, Germany

Location

St. Barbara Klinik Brustzentrum

Hamm, North Rhine-Westphalia, 59073, Germany

Location

Klinikum Leverkusen Medizinische Klinik 3

Leverkusen, North Rhine-Westphalia, 51375, Germany

Location

Praxis für gynäkologische Onkologie am Ev. Krankenhaus Bethesda

Mönchengladbach, North Rhine-Westphalia, 41061, Germany

Location

St. Franziskus-Hospital Brustzentrum

Münster, North Rhine-Westphalia, 48145, Germany

Location

Universitätsklinikum Frauenheilkunde

Münster, North Rhine-Westphalia, 48149, Germany

Location

ONCOLOGIANOVA Praxis Dr. Emde

Recklinghausen, North Rhine-Westphalia, 45659, Germany

Location

Marienkrankenhaus Schwerte Brustzentrum

Schwerte, North Rhine-Westphalia, 58239, Germany

Location

Marien-Krankenhaus Klinik für Gynäkologie und Geburtshilfe

Siegen, North Rhine-Westphalia, 57072, Germany

Location

Diakonie Klinikum Jung Stilling Brustzentrum

Siegen, North Rhine-Westphalia, 57074, Germany

Location

Praxisnetz Hämatologie / internistische Onkologie Praxis Troisdorf

Troisdorf, North Rhine-Westphalia, 53840, Germany

Location

Christliches Klinikum Unna gGmbH Brustzentrum

Unna, North Rhine-Westphalia, 59423, Germany

Location

Praxis für Hämatologie und internistische Onkologie Praxis Dr. Nusch

Velbert, North Rhine-Westphalia, 42551, Germany

Location

Marien Hospital / Senologie Brustzentrum

Witten, North Rhine-Westphalia, 58452, Germany

Location

Helios Universitätsklinikum Frauenheilkunde & Geburtshilfe

Wuppertal, North Rhine-Westphalia, 42283, Germany

Location

Katholisches Klinikum Koblenz-Montabaur-Marienhof Koblenz Marienhof Koblenz - Gynäkologie

Koblenz, Rhineland-Palatinate, 56073, Germany

Location

Klinikum Mutterhaus der Borromäerinnen Innere Medizin I / Onkologie

Trier, Rhineland-Palatinate, 54290, Germany

Location

Universitätsklinikum des Saarlandes Frauenklinik

Homburg, Saarland, 66421, Germany

Location

DRK Kliniken Saar / Krankenhaus Saarlouis Brustzentrum

Saarlouis, Saarland, 66740, Germany

Location

Klinikum Chemnitz Frauenklinik / Brustzentrum

Chemnitz, Saxony, 09116, Germany

Location

Universitätsklinikum Dresden Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Leipzig Gynäkologie und Universitäres Krebszentrum; Klinik und Poliklinik für Frauenheilkunde

Leipzig, Saxony, 04015, Germany

Location

Kliniken St. Georg Klinik für Gynäkologie und Geburtshilfe

Leipzig, Saxony, 04129, Germany

Location

Klinikum Obergöltzsch-Rodewisch Frauenklinik

Rodewisch, Saxony, 08228, Germany

Location

Universitätsklinikum Halle Universitätsklinik für Gynäkologie

Halle, Saxony-Anhalt, 06120, Germany

Location

Altmark-Klinikum Salzwedel Klinik für Frauenheilkunde

Salzwedel, Saxony-Anhalt, 29410, Germany

Location

Johanniter Frauenklinik Stendal Gynäkologie

Stendal, Saxony-Anhalt, 39576, Germany

Location

Universitätsklinikum Schleswig-Holstein Campus Lübeck, Frauenklinik

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Universitätsklinikum Jena Klinik und Poliklinik für Frauenheilkunde und Fortpflanzungsmedizin

Jena, Thuringia, 07747, Germany

Location

MVZ Nordhausen Praxis Dr. Andrea Grafe

Nordhausen, Thuringia, 99734, Germany

Location

Charité Berlin, Klinik für Gynäkologie m.S. Senologie Brustzentrum (CCM)

Berlin, 10117, Germany

Location

St. Gertrauden Krankenhaus Brustzentrum City Berlin

Berlin, 10713, Germany

Location

Vivantes Klinikum Am Urban Brustzentrum

Berlin, 10967, Germany

Location

DRK Klinikum Berlin-Köpenick Brustzentrum

Berlin, 12559, Germany

Location

Evangelisches Waldkrankenhaus Spandau Klinik für Gynäkologie und Geburtshilfe

Berlin, 13589, Germany

Location

Hämatologisch/Onkologische Schwerpunktpraxis Praxis Dr. Schreiber

Bremen, 28209, Germany

Location

UKE Hamburg / Frauenklinik Brustzentrum am UKE

Hamburg, 20246, Germany

Location

Agaplesion Diakonieklinikum Hamburg Frauenklinik, Brustzentrum u. Gyn. Tumorzentrum / Gyn. Studienambulanz

Hamburg, 20259, Germany

Location

Mammazentrum Hamburg am Krankenhaus Jerusalem

Hamburg, 20357, Germany

Location

Related Publications (1)

• 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.

  PMID: 37695655 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Tablets

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Nadia Harbeck, Prof. Dr.

  Ludwigs-Maximilians-University Munich, Breast Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, interventional, prospective, two-arm, randomized, open-label, controlled (neo)adjuvant, phase-III trial evaluating the efficacy and safety of ribociclib combined with endocrine therapy (ET) versus standard-of-care chemotherapy in early breast cancer (EBC) patients with molecular HR+/HER2- subtype.

Study Record Dates

• First Submitted: July 22, 2019
• First Posted: August 13, 2019
• Study Start: July 2, 2019
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Within 1 year after end of study.
• Access Criteria: for regulatory use only

Locations

DE (86)