Postoperative Use of Zoledronic Acid in Breast Cancer Patients After Neoadjuvant Chemotherapy
- Registration Number
- NCT00512993
- Lead Sponsor
- German Breast Group
- 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
- Detailed Description
The study is restricted to patients having had primary systemic chemotherapy for stage II and III breast cancer. Participation in a preoperative chemotherapy trial investigating anthracycline and taxane based regimen is allowed, but not mandatory for all patients. Patients must have significant remaining tumor tissue in the breast and/or axillary lymph node. This implies resistance to further chemotherapy and a clinically relevant risk for relapse. Bisphosphonates have a distinct mechanism of action and have demonstrated efficacy in the treatment of breast cancer with metastasis to the bone as well as adjuvant treatment after surgery of primary breast cancer. The 3rd generation bisphosphonate zoledronic acid has a favorable toxicity profile and can be conveniently given to patients over a long term period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 654
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Zoledronic acid Patients receive zoledronic acid (4mg) for 5 years. Additionally patients receive standard endocrine, radiologic and trastuzumab treatment, respectively
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method The bone-metastasis free-survival in both arms. 5 years The overall survival in both treatment arms. 5 years The toxicity of and compliance to zoledronic acid. 5 years The prognostic impact of chemotherapy induced amenorrhea in premenopausal patients. 5 years The EFS with respect to the interval between surgery and randomization. 5 years The predictive value of primary breast tumor response on the effect of postoperative treatment. 5 years
Trial Locations
- Locations (92)
LKH-Univ. Klinikum Graz, Onkologie
🇦🇹Graz, Styria, Austria
LKH Salzburg, Uni.klinik f. Innere Med. III/Onkol. Amb.
🇦🇹Salzburg, Austria
Frauenklinik Rheinfelden
🇩🇪Rheinfelden, Baden-Württemberg, Germany
Allgemeines Krankenhaus der Stadt Linz, Innere Medizin 3/Zentrum f. Häm. u. Med. Onkologie
🇦🇹Linz, Upper Austria, Austria
Universitätsklinikum Mannheim, Frauenklinik
🇩🇪Mannheim, Baden-Württemberg, Germany
Klinikum am Steinenberg
🇩🇪Reutlingen, Baden-Württemberg, Germany
Landeskrankenhaus Steyr, 2. Med. Abt. Onkologie
🇦🇹Steyr, Upper Austria, Austria
Landeskrankenhaus Feldkirch
🇦🇹Rankweil, Vorarlberg, Austria
St. Vincentius Kliniken Karlsruhe
🇩🇪Karlsruhe, Baden-Württemberg, Germany
Ostalb-Klinikum, ABC Brustzentrum, Frauenklinik
🇩🇪Aalen, Baden-Württemberg, Germany
Onkol. Schwerpunktpraxis Dr. Knoblich
🇩🇪Lörrach, Baden-Württemberg, Germany
Krankenhaus Siloah, Gynäkologie und Geburtshilfe
🇩🇪Pforzheim, Baden-Württemberg, Germany
Praxis Dr. Gottschalk, Fachärztin für Frauenheilkunde und Geburtshilfe
🇩🇪Bernau, Brandenburg, Germany
Krankenhaus Bad Cannstatt, Frauenklinik
🇩🇪Stuttgart, Baden-Württemberg, Germany
Universitätsklinikum Tübingen, Frauenklinik
🇩🇪Tübingen, Baden-Württemberg, Germany
Schwerpunktpraxis der Gynäkologie und Onkologie
🇩🇪Fuerstenwalde, Brandenburg, Germany
Ruppiner Kliniken, Frauenklinik
🇩🇪Neuruppin, Brandenburg, Germany
Universität Greifswald, Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Greifswald, Mecklenburg-Vorpommern, Germany
Dietrich-Bonhoeffer Klinikum, Frauenklinik
🇩🇪Neubrandenburg, Mecklenburg-Vorpommern, Germany
Kreiskrankenhaus Ebersberg, Gynäkologisch-onkologische Abteilung
🇩🇪Ebersberg, Bayern, Germany
Alfried-Krupp-Krankenhaus, Frauenklinik
🇩🇪Essen, Nordrhein-Westfalen, Germany
Caritas-Krankenhaus St. Josef, Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Regensburg, Bayern, Germany
Klinikum Kassel GmbH, Gynäkologische Ambulanz
🇩🇪Kassel, Hessen, Germany
Vinzenzkrankenhaus, Gynäkologie
🇩🇪Hannover, Niedersachsen, Germany
Onkologische Schwerpunktpraxis, Dres. Schäfer / Just / Görner
🇩🇪Bielefeld, Nordrhein-Westfalen, Germany
Gynäkologische Praxis Dr. Deertz
🇩🇪Essen, Nordrhein-Westfalen, Germany
Uniklinikum, Klinik für Geburtshilfe und Gynäkologie
🇩🇪Mainz, Rheinland-Pfalz, Germany
Klinikum Stadt Hanau
🇩🇪Hanau, Hessen, Germany
Klinikum Wels-Grieskirchen GmbH, Abt. f. Innere Medizin IV
🇦🇹Wels, Upper Austria, Austria
Asklepios Paulinen Klinik, Frauenklinik
🇩🇪Wiesbaden, Hessen, Germany
Gemeinschaftspraxis Gynäkologie
🇩🇪Hildesheim, Niedersachsen, Germany
Luisenkrankenhaus, Senologie, Brustzentrum
🇩🇪Düsseldorf, Nordrhein-Westfalen, Germany
Marienhospital Altenessen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Medizinische Universität Wien
🇦🇹Wien, Lower Austria, Austria
Praxis für Innere Medizin, Hämatologie, internistische Onkologie
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Hermann-Josef Krankenhaus, Frauenklinik
🇩🇪Erkelenz, Nordrhein-Westfalen, Germany
St. Antonius Hospital, Klinik für Hämatologie u. Onkologie
🇩🇪Eschweiler, Nordrhein-Westfalen, Germany
Schwerpunktpraxis, Internistisch-gynäkolog.-onkolog.
🇩🇪Lüneburg, Niedersachsen., Germany
Krankenhaus Cuxhaven, Frauenklinik
🇩🇪Cuxhaven, Niedersachsen, Germany
SRH Wald-Klinikum Gera gGmbH, Brustzentrum Ostthüringen
🇩🇪Gera, Thüringen, Germany
Städt. Kliniken Frankfurt-Höchst, Frauenklinik
🇩🇪Frankfurt/Höchst, Hessen, Germany
St. Markus Krankenhaus, Frauenklinik
🇩🇪Frankfurt, Hessen, Germany
Klinikum Rosenheim, Abt. Gynäkologie u. Geburtshilfe
🇩🇪Rosenheim, Bayern, Germany
Schwerpunktpraxis Gynäkologie, Onkologie, Naturheilverfahren
🇩🇪Berlin-Tempelhof, Berlin, Germany
Intern. Gemeinschaftspraxis
🇩🇪Friedrichshafen, Germany
GBG Forschungs GmbH
🇩🇪Neu-Isenburg, Hessen, Germany
Praxisklinik, Krebsheilkunde für Frauen / Brustzentrum
🇩🇪Berlin, Germany
Universitätsklinikum Erlangen, Frauenklinik mit Poliklinik
🇩🇪Erlangen, Bayern, Germany
St. Josefs-Hospital, Gynäkologie und Geburtshilfe
🇩🇪Wiesbaden, Hessen, Germany
Dr.-Horst-Schmidt-Kliniken GmbH, Klinik f. Gyn. und gyn. Onkologie
🇩🇪Wiesbaden, Hessen, Germany
Henriettenstiftung
🇩🇪Hannover, Niedersachsen, Germany
Onkologische Schwerpunktpraxis Dr. Glados, Hämatologie / Internistische Onkologie
🇩🇪Coesfeld, Nordrhein-Westfalen, Germany
Marienhospital Witten, Brustzentrum
🇩🇪Witten, Nordrhein-Westfalen, Germany
DRK Kliniken Köpenick, Frauenklinik
🇩🇪Berlin, Germany
Krankenhaus Neunkirchen gGmbH, Frauenklinik
🇩🇪Neunkirchen, Saarland, Germany
Elisabeth-Hospital, Frauenklinik
🇩🇪Ibbenbüren, Nordrhein-Westfalen, Germany
St. Vincenz und Elisabeth-Hospital
🇩🇪Mainz, Rheinland-Pfalz, Germany
Klinikum der Universität zu Köln
🇩🇪Köln, Nordrhein-Westfalen, Germany
Johanniter-Krankenhaus Genthin-Stendal GmbH, Frauenheilkunde und Geburtshilfe
🇩🇪Stendal, Sachsen-Anhalt, Germany
Onkologische Schwerpunktpraxis
🇩🇪Bremen, Germany
Krankenhaus Salzwedel
🇩🇪Salzwedel, Germany
Klinikum Quedlinburg, Frauenklinik
🇩🇪Quedlinburg, Sachsen-Anhalt, Germany
Technische Universität Dresden
🇩🇪Dresden, Sachsen, Germany
Universitätsklinikum, Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Jena, Thüringen, Germany
Evangelisches Diakonie-Krankenhaus, Frauenklinik
🇩🇪Bremen, Germany
A. ö. Krankenhaus der Barmherzigen Brüder, Interne Abteilung
🇦🇹St. Veit a. d. Glan, Carinthia, Austria
Ostholstein Kliniken GmbH Klinik Oldenburg, Zentrum für Gynäkologie und Geburtshilfe Sana Kliniken Ostholstein
🇩🇪Oldenburg, Schleswig-Holstein, Germany
Landeskrankenhaus Wolfsberg, Chirurgische Abteilung
🇦🇹Wolfsberg, Carinthia, Austria
Universitätsklinikum Schleswig-Holstein Campus Kiel
🇩🇪Kiel, Schleswig-Holstein, Germany
Asklepios-Klinik Lich, Frauenklinik
🇩🇪Lich, Hessen, Germany
Allgm. Krankenhaus Celle, Frauenklinik
🇩🇪Celle, Niedersachsen, Germany
Kreiskrankenhaus Gifhorn, Interdisziplinäres Brustzentrum
🇩🇪Gifhorn, Niedersachsen, Germany
St. Vincenz Krankenhaus, Frauenklinik
🇩🇪Limburg, Hessen, Germany
Universitätsklinikum, Frauenklinik / Mutter-Kind-Zentrum
🇩🇪Marburg, Hessen, Germany
Klinikum Schaumburg, Kreiskrankenhaus Stadthagen, Gynäkologie und Geburtshilfe
🇩🇪Stadhagen, Niedersachsen, Germany
Facharzt für Frauenheilkunde und Geburtshilfe
🇩🇪Hamburg, Germany
Onkologische Schwerpunktpraxis Dr. Tessen
🇩🇪Goslar, Niedersachsen, Germany
Klinikum der Otto-v.-Guericke-Universität, Frauenklinik
🇩🇪Magdeburg, Sachsen-Anhalt, Germany
Krankenhaus St. Elisabeth und St. Barbara Halle, Klinik für Gynäkologie und Geburtshilfe
🇩🇪Halle / Saale, Sachsen-Anhalt, Germany
Klinikum Chemnitz gGmbH, Frauenklinik
🇩🇪Chemnitz, Sachsen, Germany
Gemeinschaftspraxis, Fachärzte für Innere Medizin, Hämatologie und Internistische Onkologie
🇩🇪Dresden, Sachsen, Germany
Onkologie Bethanien, Onkologie / Tagesklinik
🇩🇪Frankfurt, Hessen, Germany
Asklepios Klinik, Frauenklinik
🇩🇪Langen, Hessen, Germany
Universitäts Klinikum Innsbruck
🇦🇹Innsbruck, Tirol, Austria
St. Elisabeth-KKH, Brustzentrum Koeln-Hohenlind
🇩🇪Köln, Nordrhein-Westfalen, Germany
Kreiskrankenhaus Hameln, Brustzentrum
🇩🇪Hameln, Niedersachsen, Germany
Klinikum der Universität zu Köln, Klinik und Poliklinik für Gyn. und Geburtshilfe
🇩🇪Köln, Nordrhein-Westfalen, Germany
Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Essen, Nordrhein-Westfalen, Germany
Marienhospital Herne, Onkologische / Hämatologische Ambulanz
🇩🇪Herne, Nordrhein-Westfalen, Germany
Klinikum Sindelfingen-Böblingen / Kliniken Böblingen, Frauenklinik
🇩🇪Böblingen, Baden-Württemberg, Germany
Klinikum Südstadt, Universitätsfrauenklinik
🇩🇪Rostock, Mecklenburg-Vorpommern, Germany
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Schleswig-Holstein, Germany