Postoperative Use of Zoledronic Acid in Breast Cancer Patients After Neoadjuvant Chemotherapy

NCT ID: NCT00512993

Last Updated: 2015-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 654 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2013-11-30

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Patients receive zoledronic acid (4mg) for 5 years. Additionally patients receive standard endocrine, radiologic and trastuzumab treatment, respectively

Group Type: ACTIVE_COMPARATOR

Zoledronic acid

Intervention Type: DRUG

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

Observation

Patients will be under observation and receive standard endocrine, radiologic and trastuzumab treatment, respectively

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Zoledronic acid

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

Intervention Type: DRUG

Other Intervention Names

Zometa

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Austrian Breast & Colorectal Cancer Study Group

NETWORK

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

GBG Forschungs GmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gunter von Minckwitz, Prof. MD

Role: STUDY_CHAIR

GBG Forschungs GmbH, Hessen, Germany

Peter Dubsky, MD

Role: STUDY_CHAIR

Austrian Breast & Colorectal Cancer Study Group

Locations

Universitätsklinikum Schleswig-Holstein

Lübeck, Schleswig-Holstein, Germany

A. ö. Krankenhaus der Barmherzigen Brüder, Interne Abteilung

Saint Veit A. D. Glan, Carinthia, Austria

Landeskrankenhaus Wolfsberg, Chirurgische Abteilung

Wolfsberg, Carinthia, Austria

Medizinische Universität Wien

Wien, Lower Austria, Austria

LKH Salzburg, Uni.klinik f. Innere Med. III/Onkol. Amb.

Salzburg, Salzburg, Austria

LKH-Univ. Klinikum Graz, Onkologie

Graz, Styria, Austria

Universitäts Klinikum Innsbruck

Innsbruck, Tyrol, Austria

Allgemeines Krankenhaus der Stadt Linz, Innere Medizin 3/Zentrum f. Häm. u. Med. Onkologie

Linz, Upper Austria, Austria

Landeskrankenhaus Steyr, 2. Med. Abt. Onkologie

Steyr, Upper Austria, Austria

Klinikum Wels-Grieskirchen GmbH, Abt. f. Innere Medizin IV

Wels, Upper Austria, Austria

Landeskrankenhaus Feldkirch

Rankweil, Vorarlberg, Austria

Ostalb-Klinikum, ABC Brustzentrum, Frauenklinik

Aalen, Baden-Wurttemberg, Germany

Klinikum Sindelfingen-Böblingen / Kliniken Böblingen, Frauenklinik

Böblingen, Baden-Wurttemberg, Germany

St. Vincentius Kliniken Karlsruhe

Karlsruhe, Baden-Wurttemberg, Germany

Onkol. Schwerpunktpraxis Dr. Knoblich

Loerrach, Baden-Wurttemberg, Germany

Universitätsklinikum Mannheim, Frauenklinik

Mannheim, Baden-Wurttemberg, Germany

Krankenhaus Siloah, Gynäkologie und Geburtshilfe

Pforzheim, Baden-Wurttemberg, Germany

Klinikum am Steinenberg

Reutlingen, Baden-Wurttemberg, Germany

Frauenklinik Rheinfelden

Rheinfelden, Baden-Wurttemberg, Germany

Krankenhaus Bad Cannstatt, Frauenklinik

Stuttgart, Baden-Wurttemberg, Germany

Universitätsklinikum Tübingen, Frauenklinik

Tübingen, Baden-Wurttemberg, Germany

Kreiskrankenhaus Ebersberg, Gynäkologisch-onkologische Abteilung

Ebersberg, Bavaria, Germany

Universitätsklinikum Erlangen, Frauenklinik mit Poliklinik

Erlangen, Bavaria, Germany

Caritas-Krankenhaus St. Josef, Klinik für Frauenheilkunde und Geburtshilfe

Regensburg, Bavaria, Germany

Klinikum Rosenheim, Abt. Gynäkologie u. Geburtshilfe

Rosenheim, Bavaria, Germany

Praxis Dr. Gottschalk, Fachärztin für Frauenheilkunde und Geburtshilfe

Bernau bei Berlin, Brandenburg, Germany

Schwerpunktpraxis der Gynäkologie und Onkologie

Fürstenwalde, Brandenburg, Germany

Ruppiner Kliniken, Frauenklinik

Neuruppin, Brandenburg, Germany

Onkologische Schwerpunktpraxis

Bremen, City state Bremen, Germany

Evangelisches Diakonie-Krankenhaus, Frauenklinik

Bremen, City state Bremen, Germany

Facharzt für Frauenheilkunde und Geburtshilfe

Hamburg, City state of Hamburg, Germany

Onkologie Bethanien, Onkologie / Tagesklinik

Frankfurt am Main, Hesse, Germany

St. Markus Krankenhaus, Frauenklinik

Frankfurt am Main, Hesse, Germany

Städt. Kliniken Frankfurt-Höchst, Frauenklinik

Frankfurt/Höchst, Hesse, Germany

Klinikum Stadt Hanau

Hanau, Hesse, Germany

Klinikum Kassel GmbH, Gynäkologische Ambulanz

Kassel, Hesse, Germany

Asklepios Klinik, Frauenklinik

Langen, Hesse, Germany

Asklepios-Klinik Lich, Frauenklinik

Lich, Hesse, Germany

St. Vincenz Krankenhaus, Frauenklinik

Limburg an der Lahn, Hesse, Germany

Universitätsklinikum, Frauenklinik / Mutter-Kind-Zentrum

Marburg, Hesse, Germany

GBG Forschungs GmbH

Neu-Isenburg, Hesse, Germany

St. Josefs-Hospital, Gynäkologie und Geburtshilfe

Wiesbaden, Hesse, Germany

Asklepios Paulinen Klinik, Frauenklinik

Wiesbaden, Hesse, Germany

Dr.-Horst-Schmidt-Kliniken GmbH, Klinik f. Gyn. und gyn. Onkologie

Wiesbaden, Hesse, Germany

Allgm. Krankenhaus Celle, Frauenklinik

Celle, Lower Saxony, Germany

Krankenhaus Cuxhaven, Frauenklinik

Cuxhaven, Lower Saxony, Germany

Kreiskrankenhaus Gifhorn, Interdisziplinäres Brustzentrum

Gifhorn, Lower Saxony, Germany

Onkologische Schwerpunktpraxis Dr. Tessen

Goslar, Lower Saxony, Germany

Kreiskrankenhaus Hameln, Brustzentrum

Hamelin, Lower Saxony, Germany

Henriettenstiftung

Hanover, Lower Saxony, Germany

Vinzenzkrankenhaus, Gynäkologie

Hanover, Lower Saxony, Germany

Gemeinschaftspraxis Gynäkologie

Hildesheim, Lower Saxony, Germany

Facharzt für Frauenheilkunde und Geburtshilfe

Ilsede, Lower Saxony, Germany

Schwerpunktpraxis, Internistisch-gynäkolog.-onkolog.

Lüneburg, Lower Saxony, Germany

Klinikum Schaumburg, Kreiskrankenhaus Stadthagen, Gynäkologie und Geburtshilfe

Stadhagen, Lower Saxony, Germany

Universität Greifswald, Klinik für Frauenheilkunde und Geburtshilfe

Greifswald, Mecklenburg-Vorpommern, Germany

Dietrich-Bonhoeffer Klinikum, Frauenklinik

Neubrandenburg, Mecklenburg-Vorpommern, Germany

Klinikum Südstadt, Universitätsfrauenklinik

Rostock, Mecklenburg-Vorpommern, Germany

Onkologische Schwerpunktpraxis, Dres. Schäfer / Just / Görner

Bielefeld, North Rhine-Westphalia, Germany

Praxis für Innere Medizin, Hämatologie, internistische Onkologie

Bochum, North Rhine-Westphalia, Germany

Onkologische Schwerpunktpraxis Dr. Glados, Hämatologie / Internistische Onkologie

Coesfeld, North Rhine-Westphalia, Germany

Klinikum der Universität zu Köln, Klinik und Poliklinik für Gyn. und Geburtshilfe

Cologne, North Rhine-Westphalia, Germany

Klinikum der Universität zu Köln

Cologne, North Rhine-Westphalia, Germany

St. Elisabeth-KKH, Brustzentrum Koeln-Hohenlind

Cologne, North Rhine-Westphalia, Germany

Luisenkrankenhaus, Senologie, Brustzentrum

Düsseldorf, North Rhine-Westphalia, Germany

Hermann-Josef Krankenhaus, Frauenklinik

Erkelenz, North Rhine-Westphalia, Germany

St. Antonius Hospital, Klinik für Hämatologie u. Onkologie

Eschweiler, North Rhine-Westphalia, Germany

Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe

Essen, North Rhine-Westphalia, Germany

Gynäkologische Praxis Dr. Deertz

Essen, North Rhine-Westphalia, Germany

Alfried-Krupp-Krankenhaus, Frauenklinik

Essen, North Rhine-Westphalia, Germany

Marienhospital Altenessen

Essen, North Rhine-Westphalia, Germany

Marienhospital Herne, Onkologische / Hämatologische Ambulanz

Herne, North Rhine-Westphalia, Germany

Elisabeth-Hospital, Frauenklinik

Ibbenbueren, North Rhine-Westphalia, Germany

Marienhospital Witten, Brustzentrum

Witten, North Rhine-Westphalia, Germany

St. Vincenz und Elisabeth-Hospital

Mainz, Rhineland-Palatinate, Germany

Uniklinikum, Klinik für Geburtshilfe und Gynäkologie

Mainz, Rhineland-Palatinate, Germany

Krankenhaus Neunkirchen gGmbH, Frauenklinik

Neunkirchen, Saarland, Germany

Klinikum Chemnitz gGmbH, Frauenklinik

Chemnitz, Saxony, Germany

Gemeinschaftspraxis, Fachärzte für Innere Medizin, Hämatologie und Internistische Onkologie

Dresden, Saxony, Germany

Technische Universität Dresden

Dresden, Saxony, Germany

Krankenhaus St. Elisabeth und St. Barbara Halle, Klinik für Gynäkologie und Geburtshilfe

Halle, Saxony-Anhalt, Germany

Klinikum der Otto-v.-Guericke-Universität, Frauenklinik

Magdeburg, Saxony-Anhalt, Germany

Klinikum Quedlinburg, Frauenklinik

Quedlinburg, Saxony-Anhalt, Germany

Johanniter-Krankenhaus Genthin-Stendal GmbH, Frauenheilkunde und Geburtshilfe

Stendal, Saxony-Anhalt, Germany

Universitätsklinikum Schleswig-Holstein Campus Kiel

Kiel, Schleswig-Holstein, Germany

Ostholstein Kliniken GmbH Klinik Oldenburg, Zentrum für Gynäkologie und Geburtshilfe Sana Kliniken Ostholstein

Oldenburg in Holstein, Schleswig-Holstein, Germany

Praxisklinik, Krebsheilkunde für Frauen / Brustzentrum

Berlin, State of Berlin, Germany

DRK Kliniken Köpenick, Frauenklinik

Berlin, State of Berlin, Germany

Schwerpunktpraxis Gynäkologie, Onkologie, Naturheilverfahren

Tempelhof, State of Berlin, Germany

SRH Wald-Klinikum Gera gGmbH, Brustzentrum Ostthüringen

Gera, Thuringia, Germany

Universitätsklinikum, Klinik für Frauenheilkunde und Geburtshilfe

Jena, Thuringia, Germany

Intern. Gemeinschaftspraxis

Friedrichshafen, , Germany

Krankenhaus Salzwedel

Salzwedel, , Germany

Countries

Austria; Germany

References

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.

Reference Type: DERIVED

PMID: 38979716 (View on PubMed)

Related Links

http://www.germanbreastgroup.de

Related Info

Other Identifiers

NATAN

Identifier Type: -

Identifier Source: secondary_id

ABCSG 29

Identifier Type: -

Identifier Source: secondary_id

GBG 36

Identifier Type: -

Identifier Source: org_study_id