Postoperative Use of Zoledronic Acid in Breast Cancer Patients After Neoadjuvant Chemotherapy
NATAN
A Randomized, Multicenter, Open Phase III Study Comparing the Postoperative Use of Zoledronic Acid Versus no Treatment in Patients With Histological Tumor Residuals After Preoperative Anthracycline and Taxane Containing Chemotherapy for Primary Breast Cancer
3 other identifiers
interventional
654
2 countries
93
Brief Summary
The purpose of this study is to determine the event-free survival (EFS) after zoledronic acid for 5 years versus no postoperative treatment in patients with "chemo-insensitive" breast cancer (ypT1-4 and/or ypN1-3) after preoperative anthracycline/taxane containing chemotherapy
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 breast-cancer
Started Dec 2004
Typical duration for phase_3 breast-cancer
93 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2004
CompletedFirst Submitted
Initial submission to the registry
August 3, 2007
CompletedFirst Posted
Study publicly available on registry
August 8, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2013
CompletedMarch 5, 2015
March 1, 2015
8.9 years
August 3, 2007
March 4, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The event-free survival (EFS) after zoledronic acid for 5 years versus no postoperative treatment in patients with "chemo-insensitive" breast cancer (ypT1-4 and/or ypN1-3) after preoperative anthracycline/taxane containing chemotherapy.
5 years
Secondary Outcomes (6)
The overall survival in both treatment arms.
5 years
The EFS with respect to the interval between surgery and randomization.
5 years
The bone-metastasis free-survival in both arms.
5 years
The toxicity of and compliance to zoledronic acid.
5 years
The predictive value of primary breast tumor response on the effect of postoperative treatment.
5 years
- +1 more secondary outcomes
Study Arms (2)
Treatment
ACTIVE COMPARATORPatients receive zoledronic acid (4mg) for 5 years. Additionally patients receive standard endocrine, radiologic and trastuzumab treatment, respectively
Observation
NO INTERVENTIONPatients will be under observation and receive standard endocrine, radiologic and trastuzumab treatment, respectively
Interventions
Infusion of zoledronic acid (4 mg) every 4 weeks for six doses, followed by every 3 months for 8 doses, followed by every 6 months for 5 doses
Eligibility Criteria
You may qualify if:
- Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures;
- Complete baseline documentation sent to GBG;
- Prior preoperative chemotherapy for at least 4 cycles, of which at least two must contain a taxane and an anthracycline;
- Completely resected unilateral or bilateral primary carcinoma of the breast with histologically detectable tumor residuals (ypT1-4) and/or histology confirmed involvement of axillary nodes (ypN1-3). Sentinel node biopsy is allowed, but complete axillary clearance is mandatory in node positive cases;
- A maximum interval of 3 years from date of axillary surgery to entering this trial;
- Age 18 years or older;
- Karnofsky index \>= 70%;
- Life expectancy of at least 10 years, disregarding the diagnosis of cancer;
- No clinical evidence of local recurrence or distant metastases. Complete staging work-up: All patients must have breast ultrasound, chest X-ray, ultrasound or CT scan of the liver within 3 months prior to registration, as well as (bilateral) mammography or breast MRI and bone scan within 8 months prior to registration. In case of a positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated;
- Adequate renal and hepatic function (serum creatinine, bilirubin, and transaminases within 1.5 × upper normal range);
- Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating center.
You may not qualify if:
- Known hypersensitivity reaction to the investigational compound;
- Prior postoperative chemotherapy;
- Prior treatment with bisphosphonates since breast cancer surgery;
- Pregnant or lactating patients. Patients of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to registration and must implement adequate non-hormonal contraceptive measures (barrier methods, intra uterine contraceptive devices, sterilization) during study treatment;
- History of diseases with influence on bone metabolism, such as Paget's disease of bone and primary hyperparathyroidism or osteoporosis requiring treatment at the time of study entry or considered likely to become necessary within the six months
- Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study
- Prior or concomitant secondary malignancy (except non-melanomatous skin cancer or carcinoma in situ of the uterine cervix)
- Concurrent treatment with other experimental drugs or any other anti-cancer therapy;
- Abnormal renal function as evidenced by a calculated creatinine clearance \< 30 ml/minute;
- Serum calcium concentration \< 8.0 mg/dl (2.00 mmol/L) or \> 12.0 mg/dl (3.00 mmol/L)
- Concurrent treatment with sex hormones. Prior treatment must be stopped before study entry;
- Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw, of exposed bone in the mouth, or of slow healing after dental procedures.
- Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)
- Male patients.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GBG Forschungs GmbHlead
- Austrian Breast & Colorectal Cancer Study Groupcollaborator
- Novartis Pharmaceuticalscollaborator
Study Sites (93)
A. ö. Krankenhaus der Barmherzigen Brüder, Interne Abteilung
Saint Veit A. D. Glan, Carinthia, A-9300, Austria
Landeskrankenhaus Wolfsberg, Chirurgische Abteilung
Wolfsberg, Carinthia, A-9400, Austria
Medizinische Universität Wien
Wien, Lower Austria, Austria
LKH Salzburg, Uni.klinik f. Innere Med. III/Onkol. Amb.
Salzburg, Salzburg, A-5020, Austria
LKH-Univ. Klinikum Graz, Onkologie
Graz, Styria, A-8036, Austria
Universitäts Klinikum Innsbruck
Innsbruck, Tyrol, 6020, Austria
Allgemeines Krankenhaus der Stadt Linz, Innere Medizin 3/Zentrum f. Häm. u. Med. Onkologie
Linz, Upper Austria, A-4020, Austria
Landeskrankenhaus Steyr, 2. Med. Abt. Onkologie
Steyr, Upper Austria, A-4400, Austria
Klinikum Wels-Grieskirchen GmbH, Abt. f. Innere Medizin IV
Wels, Upper Austria, A-4600, Austria
Landeskrankenhaus Feldkirch
Rankweil, Vorarlberg, 6830, Austria
Ostalb-Klinikum, ABC Brustzentrum, Frauenklinik
Aalen, Baden-Wurttemberg, 73430, Germany
Klinikum Sindelfingen-Böblingen / Kliniken Böblingen, Frauenklinik
Böblingen, Baden-Wurttemberg, 71032, Germany
St. Vincentius Kliniken Karlsruhe
Karlsruhe, Baden-Wurttemberg, 76135, Germany
Onkol. Schwerpunktpraxis Dr. Knoblich
Loerrach, Baden-Wurttemberg, 79539, Germany
Universitätsklinikum Mannheim, Frauenklinik
Mannheim, Baden-Wurttemberg, 68167, Germany
Krankenhaus Siloah, Gynäkologie und Geburtshilfe
Pforzheim, Baden-Wurttemberg, 75179, Germany
Klinikum am Steinenberg
Reutlingen, Baden-Wurttemberg, 72764, Germany
Frauenklinik Rheinfelden
Rheinfelden, Baden-Wurttemberg, 79618, Germany
Krankenhaus Bad Cannstatt, Frauenklinik
Stuttgart, Baden-Wurttemberg, 70374, Germany
Universitätsklinikum Tübingen, Frauenklinik
Tübingen, Baden-Wurttemberg, 72076, Germany
Kreiskrankenhaus Ebersberg, Gynäkologisch-onkologische Abteilung
Ebersberg, Bavaria, 85560, Germany
Universitätsklinikum Erlangen, Frauenklinik mit Poliklinik
Erlangen, Bavaria, 91054, Germany
Caritas-Krankenhaus St. Josef, Klinik für Frauenheilkunde und Geburtshilfe
Regensburg, Bavaria, 93053, Germany
Klinikum Rosenheim, Abt. Gynäkologie u. Geburtshilfe
Rosenheim, Bavaria, 83022, Germany
Praxis Dr. Gottschalk, Fachärztin für Frauenheilkunde und Geburtshilfe
Bernau bei Berlin, Brandenburg, 16321, Germany
Schwerpunktpraxis der Gynäkologie und Onkologie
Fürstenwalde, Brandenburg, 15517, Germany
Ruppiner Kliniken, Frauenklinik
Neuruppin, Brandenburg, 16816, Germany
Onkologische Schwerpunktpraxis
Bremen, City state Bremen, 28205, Germany
Evangelisches Diakonie-Krankenhaus, Frauenklinik
Bremen, City state Bremen, 28239, Germany
Facharzt für Frauenheilkunde und Geburtshilfe
Hamburg, Hamburg, 22041, Germany
Onkologie Bethanien, Onkologie / Tagesklinik
Frankfurt am Main, Hesse, 60389, Germany
St. Markus Krankenhaus, Frauenklinik
Frankfurt am Main, Hesse, 60431, Germany
Städt. Kliniken Frankfurt-Höchst, Frauenklinik
Frankfurt/Höchst, Hesse, 65929, Germany
Klinikum Stadt Hanau
Hanau, Hesse, 63450, Germany
Klinikum Kassel GmbH, Gynäkologische Ambulanz
Kassel, Hesse, 34125, Germany
Asklepios Klinik, Frauenklinik
Langen, Hesse, 63225, Germany
Asklepios-Klinik Lich, Frauenklinik
Lich, Hesse, 35423, Germany
St. Vincenz Krankenhaus, Frauenklinik
Limburg an der Lahn, Hesse, 65549, Germany
Universitätsklinikum, Frauenklinik / Mutter-Kind-Zentrum
Marburg, Hesse, 35043, Germany
GBG Forschungs GmbH
Neu-Isenburg, Hesse, 63263, Germany
St. Josefs-Hospital, Gynäkologie und Geburtshilfe
Wiesbaden, Hesse, 65189, Germany
Asklepios Paulinen Klinik, Frauenklinik
Wiesbaden, Hesse, 65197, Germany
Dr.-Horst-Schmidt-Kliniken GmbH, Klinik f. Gyn. und gyn. Onkologie
Wiesbaden, Hesse, 65199, Germany
Allgm. Krankenhaus Celle, Frauenklinik
Celle, Lower Saxony, 29223, Germany
Krankenhaus Cuxhaven, Frauenklinik
Cuxhaven, Lower Saxony, 27474, Germany
Kreiskrankenhaus Gifhorn, Interdisziplinäres Brustzentrum
Gifhorn, Lower Saxony, 38518, Germany
Onkologische Schwerpunktpraxis Dr. Tessen
Goslar, Lower Saxony, 38642, Germany
Kreiskrankenhaus Hameln, Brustzentrum
Hamelin, Lower Saxony, 31785, Germany
Henriettenstiftung
Hanover, Lower Saxony, 30559, Germany
Vinzenzkrankenhaus, Gynäkologie
Hanover, Lower Saxony, 30559, Germany
Gemeinschaftspraxis Gynäkologie
Hildesheim, Lower Saxony, 31134, Germany
Facharzt für Frauenheilkunde und Geburtshilfe
Ilsede, Lower Saxony, 31241, Germany
Schwerpunktpraxis, Internistisch-gynäkolog.-onkolog.
Lüneburg, Lower Saxony, 21339, Germany
Klinikum Schaumburg, Kreiskrankenhaus Stadthagen, Gynäkologie und Geburtshilfe
Stadhagen, Lower Saxony, 31655, Germany
Universität Greifswald, Klinik für Frauenheilkunde und Geburtshilfe
Greifswald, Mecklenburg-Vorpommern, 17487, Germany
Dietrich-Bonhoeffer Klinikum, Frauenklinik
Neubrandenburg, Mecklenburg-Vorpommern, 17039, Germany
Klinikum Südstadt, Universitätsfrauenklinik
Rostock, Mecklenburg-Vorpommern, 18059, Germany
Onkologische Schwerpunktpraxis, Dres. Schäfer / Just / Görner
Bielefeld, North Rhine-Westphalia, 33604, Germany
Praxis für Innere Medizin, Hämatologie, internistische Onkologie
Bochum, North Rhine-Westphalia, 44787, Germany
Onkologische Schwerpunktpraxis Dr. Glados, Hämatologie / Internistische Onkologie
Coesfeld, North Rhine-Westphalia, 48653, Germany
Klinikum der Universität zu Köln, Klinik und Poliklinik für Gyn. und Geburtshilfe
Cologne, North Rhine-Westphalia, 50924, Germany
Klinikum der Universität zu Köln
Cologne, North Rhine-Westphalia, 50924, Germany
St. Elisabeth-KKH, Brustzentrum Koeln-Hohenlind
Cologne, North Rhine-Westphalia, 50935, Germany
Luisenkrankenhaus, Senologie, Brustzentrum
Düsseldorf, North Rhine-Westphalia, 40235, Germany
Hermann-Josef Krankenhaus, Frauenklinik
Erkelenz, North Rhine-Westphalia, 41812, Germany
St. Antonius Hospital, Klinik für Hämatologie u. Onkologie
Eschweiler, North Rhine-Westphalia, 52249, Germany
Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe
Essen, North Rhine-Westphalia, 45122, Germany
Gynäkologische Praxis Dr. Deertz
Essen, North Rhine-Westphalia, 45130, Germany
Alfried-Krupp-Krankenhaus, Frauenklinik
Essen, North Rhine-Westphalia, 45131, Germany
Marienhospital Altenessen
Essen, North Rhine-Westphalia, 45329, Germany
Marienhospital Herne, Onkologische / Hämatologische Ambulanz
Herne, North Rhine-Westphalia, 44625, Germany
Elisabeth-Hospital, Frauenklinik
Ibbenbueren, North Rhine-Westphalia, 49477, Germany
Marienhospital Witten, Brustzentrum
Witten, North Rhine-Westphalia, 58452, Germany
St. Vincenz und Elisabeth-Hospital
Mainz, Rhineland-Palatinate, 55131, Germany
Uniklinikum, Klinik für Geburtshilfe und Gynäkologie
Mainz, Rhineland-Palatinate, 55131, Germany
Krankenhaus Neunkirchen gGmbH, Frauenklinik
Neunkirchen, Saarland, 66538, Germany
Klinikum Chemnitz gGmbH, Frauenklinik
Chemnitz, Saxony, 09116, Germany
Gemeinschaftspraxis, Fachärzte für Innere Medizin, Hämatologie und Internistische Onkologie
Dresden, Saxony, 01127, Germany
Technische Universität Dresden
Dresden, Saxony, 01307, Germany
Krankenhaus St. Elisabeth und St. Barbara Halle, Klinik für Gynäkologie und Geburtshilfe
Halle, Saxony-Anhalt, 06110, Germany
Klinikum der Otto-v.-Guericke-Universität, Frauenklinik
Magdeburg, Saxony-Anhalt, 39108, Germany
Klinikum Quedlinburg, Frauenklinik
Quedlinburg, Saxony-Anhalt, 06484, Germany
Johanniter-Krankenhaus Genthin-Stendal GmbH, Frauenheilkunde und Geburtshilfe
Stendal, Saxony-Anhalt, 39576, Germany
Universitätsklinikum Schleswig-Holstein Campus Kiel
Kiel, Schleswig-Holstein, 24105, Germany
Universitätsklinikum Schleswig-Holstein
Lübeck, Schleswig-Holstein, 23538, Germany
Ostholstein Kliniken GmbH Klinik Oldenburg, Zentrum für Gynäkologie und Geburtshilfe Sana Kliniken Ostholstein
Oldenburg in Holstein, Schleswig-Holstein, 23758, Germany
Praxisklinik, Krebsheilkunde für Frauen / Brustzentrum
Berlin, State of Berlin, 10367, Germany
DRK Kliniken Köpenick, Frauenklinik
Berlin, State of Berlin, 12559, Germany
Schwerpunktpraxis Gynäkologie, Onkologie, Naturheilverfahren
Tempelhof, State of Berlin, 12107, Germany
SRH Wald-Klinikum Gera gGmbH, Brustzentrum Ostthüringen
Gera, Thuringia, 07548, Germany
Universitätsklinikum, Klinik für Frauenheilkunde und Geburtshilfe
Jena, Thuringia, 07743, Germany
Intern. Gemeinschaftspraxis
Friedrichshafen, 88045, Germany
Krankenhaus Salzwedel
Salzwedel, 29410, Germany
Related Publications (1)
Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
PMID: 38979716DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Gunter von Minckwitz, Prof. MD
GBG Forschungs GmbH, Hessen, Germany
- STUDY CHAIR
Peter Dubsky, MD
Austrian Breast & Colorectal Cancer Study Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 3, 2007
First Posted
August 8, 2007
Study Start
December 1, 2004
Primary Completion
November 1, 2013
Study Completion
November 1, 2013
Last Updated
March 5, 2015
Record last verified: 2015-03