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Breast CancerPhase 3NATANNCT00512993

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

A Phase 3 study testing Zoledronic acid in people with Breast Cancer, run by GBG Forschungs GmbH at 93 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Zoledronic acid
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
654 participants
Where
93 sitesin 2 countries
Study dates
Dec 2004to Nov 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
Show all 11Show fewer
  • 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.

Who cannot join

  • 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
Show all 14Show fewer
  • 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.

Trial locations and contacts

93 sites in 2 countries.

93 sites in 2 countries

Germany83 sites

  • Ostalb-Klinikum, ABC Brustzentrum, Frauenklinik

    Aalen, Baden-Wurttemberg, 73430

  • Praxisklinik, Krebsheilkunde für Frauen / Brustzentrum

    Berlin, State of Berlin, 10367

  • DRK Kliniken Köpenick, Frauenklinik

    Berlin, State of Berlin, 12559

  • Praxis Dr. Gottschalk, Fachärztin für Frauenheilkunde und Geburtshilfe

    Bernau bei Berlin, Brandenburg, 16321

  • Onkologische Schwerpunktpraxis, Dres. Schäfer / Just / Görner

    Bielefeld, North Rhine-Westphalia, 33604

  • Klinikum Sindelfingen-Böblingen / Kliniken Böblingen, Frauenklinik

    Böblingen, Baden-Wurttemberg, 71032

  • Praxis für Innere Medizin, Hämatologie, internistische Onkologie

    Bochum, North Rhine-Westphalia, 44787

  • Onkologische Schwerpunktpraxis

    Bremen, Free Hanseatic City of Bremen, 28205

  • Evangelisches Diakonie-Krankenhaus, Frauenklinik

    Bremen, Free Hanseatic City of Bremen, 28239

  • Allgm. Krankenhaus Celle, Frauenklinik

    Celle, Lower Saxony, 29223

  • Klinikum Chemnitz gGmbH, Frauenklinik

    Chemnitz, Saxony, 09116

  • Onkologische Schwerpunktpraxis Dr. Glados, Hämatologie / Internistische Onkologie

    Coesfeld, North Rhine-Westphalia, 48653

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

    Cologne, North Rhine-Westphalia, 50924

  • Klinikum der Universität zu Köln

    Cologne, North Rhine-Westphalia, 50924

  • St. Elisabeth-KKH, Brustzentrum Koeln-Hohenlind

    Cologne, North Rhine-Westphalia, 50935

  • Krankenhaus Cuxhaven, Frauenklinik

    Cuxhaven, Lower Saxony, 27474

  • Gemeinschaftspraxis, Fachärzte für Innere Medizin, Hämatologie und Internistische Onkologie

    Dresden, Saxony, 01127

  • Technische Universität Dresden

    Dresden, Saxony, 01307

  • Luisenkrankenhaus, Senologie, Brustzentrum

    Düsseldorf, North Rhine-Westphalia, 40235

  • Kreiskrankenhaus Ebersberg, Gynäkologisch-onkologische Abteilung

    Ebersberg, Bavaria, 85560

  • Hermann-Josef Krankenhaus, Frauenklinik

    Erkelenz, North Rhine-Westphalia, 41812

  • Universitätsklinikum Erlangen, Frauenklinik mit Poliklinik

    Erlangen, Bavaria, 91054

  • St. Antonius Hospital, Klinik für Hämatologie u. Onkologie

    Eschweiler, North Rhine-Westphalia, 52249

  • Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe

    Essen, North Rhine-Westphalia, 45122

  • Gynäkologische Praxis Dr. Deertz

    Essen, North Rhine-Westphalia, 45130

  • Alfried-Krupp-Krankenhaus, Frauenklinik

    Essen, North Rhine-Westphalia, 45131

  • Marienhospital Altenessen

    Essen, North Rhine-Westphalia, 45329

  • Onkologie Bethanien, Onkologie / Tagesklinik

    Frankfurt am Main, Hesse, 60389

  • St. Markus Krankenhaus, Frauenklinik

    Frankfurt am Main, Hesse, 60431

  • Städt. Kliniken Frankfurt-Höchst, Frauenklinik

    Frankfurt/Höchst, Hesse, 65929

  • Intern. Gemeinschaftspraxis

    Friedrichshafen, 88045

  • Schwerpunktpraxis der Gynäkologie und Onkologie

    Fürstenwalde, Brandenburg, 15517

  • SRH Wald-Klinikum Gera gGmbH, Brustzentrum Ostthüringen

    Gera, Thuringia, 07548

  • Kreiskrankenhaus Gifhorn, Interdisziplinäres Brustzentrum

    Gifhorn, Lower Saxony, 38518

  • Onkologische Schwerpunktpraxis Dr. Tessen

    Goslar, Lower Saxony, 38642

  • Universität Greifswald, Klinik für Frauenheilkunde und Geburtshilfe

    Greifswald, Mecklenburg-Vorpommern, 17487

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

    Halle, Saxony-Anhalt, 06110

  • Facharzt für Frauenheilkunde und Geburtshilfe

    Hamburg, Free and Hanseatic City of Hamburg, 22041

  • Kreiskrankenhaus Hameln, Brustzentrum

    Hamelin, Lower Saxony, 31785

  • Klinikum Stadt Hanau

    Hanau, Hesse, 63450

  • Henriettenstiftung

    Hanover, Lower Saxony, 30559

  • Vinzenzkrankenhaus, Gynäkologie

    Hanover, Lower Saxony, 30559

  • Krankenhaus Salzwedel

    Hansestadt Salzwedel, 29410

  • Marienhospital Herne, Onkologische / Hämatologische Ambulanz

    Herne, North Rhine-Westphalia, 44625

  • Gemeinschaftspraxis Gynäkologie

    Hildesheim, Lower Saxony, 31134

  • Elisabeth-Hospital, Frauenklinik

    Ibbenbueren, North Rhine-Westphalia, 49477

  • Facharzt für Frauenheilkunde und Geburtshilfe

    Ilsede, Lower Saxony, 31241

  • Universitätsklinikum, Klinik für Frauenheilkunde und Geburtshilfe

    Jena, Thuringia, 07743

  • St. Vincentius Kliniken Karlsruhe

    Karlsruhe, Baden-Wurttemberg, 76135

  • Klinikum Kassel GmbH, Gynäkologische Ambulanz

    Kassel, Hesse, 34125

  • Universitätsklinikum Schleswig-Holstein Campus Kiel

    Kiel, Schleswig-Holstein, 24105

  • Asklepios Klinik, Frauenklinik

    Langen, Hesse, 63225

  • Asklepios-Klinik Lich, Frauenklinik

    Lich, Hesse, 35423

  • St. Vincenz Krankenhaus, Frauenklinik

    Limburg an der Lahn, Hesse, 65549

  • Onkol. Schwerpunktpraxis Dr. Knoblich

    Loerrach, Baden-Wurttemberg, 79539

  • Universitätsklinikum Schleswig-Holstein

    Lübeck, Schleswig-Holstein, 23538

  • Schwerpunktpraxis, Internistisch-gynäkolog.-onkolog.

    Lüneburg, Lower Saxony, 21339

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

    Magdeburg, Saxony-Anhalt, 39108

  • St. Vincenz und Elisabeth-Hospital

    Mainz, Rhineland-Palatinate, 55131

  • Uniklinikum, Klinik für Geburtshilfe und Gynäkologie

    Mainz, Rhineland-Palatinate, 55131

  • Universitätsklinikum Mannheim, Frauenklinik

    Mannheim, Baden-Wurttemberg, 68167

  • Universitätsklinikum, Frauenklinik / Mutter-Kind-Zentrum

    Marburg, Hesse, 35043

  • GBG Forschungs GmbH

    Neu-Isenburg, Hesse, 63263

  • Dietrich-Bonhoeffer Klinikum, Frauenklinik

    Neubrandenburg, Mecklenburg-Vorpommern, 17039

  • Krankenhaus Neunkirchen gGmbH, Frauenklinik

    Neunkirchen, Saarland, 66538

  • Ruppiner Kliniken, Frauenklinik

    Neuruppin, Brandenburg, 16816

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

    Oldenburg in Holstein, Schleswig-Holstein, 23758

  • Krankenhaus Siloah, Gynäkologie und Geburtshilfe

    Pforzheim, Baden-Wurttemberg, 75179

  • Klinikum Quedlinburg, Frauenklinik

    Quedlinburg, Saxony-Anhalt, 06484

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

    Regensburg, Bavaria, 93053

  • Klinikum am Steinenberg

    Reutlingen, Baden-Wurttemberg, 72764

  • Frauenklinik Rheinfelden

    Rheinfelden, Baden-Wurttemberg, 79618

  • Klinikum Rosenheim, Abt. Gynäkologie u. Geburtshilfe

    Rosenheim, Bavaria, 83022

  • Klinikum Südstadt, Universitätsfrauenklinik

    Rostock, Mecklenburg-Vorpommern, 18059

  • Klinikum Schaumburg, Kreiskrankenhaus Stadthagen, Gynäkologie und Geburtshilfe

    Stadhagen, Lower Saxony, 31655

  • Johanniter-Krankenhaus Genthin-Stendal GmbH, Frauenheilkunde und Geburtshilfe

    Stendal, Saxony-Anhalt, 39576

  • Krankenhaus Bad Cannstatt, Frauenklinik

    Stuttgart, Baden-Wurttemberg, 70374

  • Schwerpunktpraxis Gynäkologie, Onkologie, Naturheilverfahren

    Tempelhof, State of Berlin, 12107

  • Universitätsklinikum Tübingen, Frauenklinik

    Tübingen, Baden-Wurttemberg, 72076

  • St. Josefs-Hospital, Gynäkologie und Geburtshilfe

    Wiesbaden, Hesse, 65189

  • Asklepios Paulinen Klinik, Frauenklinik

    Wiesbaden, Hesse, 65197

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

    Wiesbaden, Hesse, 65199

  • Marienhospital Witten, Brustzentrum

    Witten, North Rhine-Westphalia, 58452

Other trials in Germany

Austria10 sites

  • LKH-Univ. Klinikum Graz, Onkologie

    Graz, Styria, A-8036

  • Universitäts Klinikum Innsbruck

    Innsbruck, Tyrol, 6020

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

    Linz, Upper Austria, A-4020

  • Landeskrankenhaus Feldkirch

    Rankweil, Vorarlberg, 6830

  • A. ö. Krankenhaus der Barmherzigen Brüder, Interne Abteilung

    Saint Veit A. D. Glan, Carinthia, A-9300

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

    Salzburg, State of Salzburg, A-5020

  • Landeskrankenhaus Steyr, 2. Med. Abt. Onkologie

    Steyr, Upper Austria, A-4400

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

    Wels, Upper Austria, A-4600

  • Medizinische Universität Wien

    Wien, Lower Austria

  • Landeskrankenhaus Wolfsberg, Chirurgische Abteilung

    Wolfsberg, Carinthia, A-9400

Other trials in Austria

About this study

Official title: 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

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

Read the 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
Being tested
Zoledronic acid
Keywords
Postoperative treatment with zoledronic acid, Preoperative anthracycline/taxane containing chemotherapy
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Zoledronic acidDrug

    Also called Zometa

    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

Study groups in NCT00512993
Study groupRoleWhat they receive
TreatmentActive comparatorPatients receive zoledronic acid (4mg) for 5 years. Additionally patients receive standard endocrine, radiologic and trastuzumab treatment, respectively
Receives: Drug: Zoledronic acid
ObservationNo interventionPatients will be under observation and receive standard endocrine, radiologic and trastuzumab treatment, respectively

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 5 years

Secondary outcomes (6)

  1. The overall survival in both treatment arms.

    Measured: 5 years

  2. The EFS with respect to the interval between surgery and randomization.

    Measured: 5 years

  3. The bone-metastasis free-survival in both arms.

    Measured: 5 years

  4. The toxicity of and compliance to zoledronic acid.

    Measured: 5 years

  5. The predictive value of primary breast tumor response on the effect of postoperative treatment.

    Measured: 5 years

  6. The prognostic impact of chemotherapy induced amenorrhea in premenopausal patients.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2007 (estimated)
  2. Study startDec 2004
  3. Primary completionNov 2013
  4. Study completionNov 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
654 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00512993
Sponsor's protocol ID
GBG 36
Other IDs
NATAN, ABCSG 29
Acronym
NATAN
Status last verified
Mar 2015
First submitted
3 Aug 2007
Last updated
5 Mar 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 38979716

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Zoledronic acid in people with Breast Cancer, run by GBG Forschungs GmbH at 93 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 93 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00512993, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2015.

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