Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery (INSEMA)

December 16, 2022 updated by: Toralf Reimer, MD PhD, University of Rostock

Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery in Patients With Early-stage Invasive Breast Cancer and Breast-conserving Surgery: a Randomized Prospective Surgical Trial. Intergroup-Sentinel-Mamma (INSEMA)-Trial

Although there is no doubt that the presence of lymph node metastases worsens prognosis of a patient, unambiguous evidence to support lymph node dissection is still lacking. For many solid tumors, the role of lymph node dissection is yet controversial, and may depend on the tumor type and the stage of patient presentation for diagnosis. Axillary surgery for breast cancer is now considered as staging procedure that does not seem to influence breast cancer mortality. Women with breast cancer have benefitted greatly from a series of carefully performed randomized controlled trial focusing on axillary surgery. The objective of INSEMA is to show that less axillary surgery is better, in that oncological outcomes are the same and less surgical intervention will result in fewer surgical complications.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Currently, axillary surgery for breast cancer is considered as staging procedure that does not seem to influence breast cancer mortality, since the risk of developing metastasis depends mainly on the biological behaviour of the primary (seed-and-soil model). Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement.

The goal of the present study is to show that early-stage breast cancer patients with reduced extent of axillary surgery are not inferior regarding disease-free survival outcome compared with the standard arm. All patients will be first randomized to either no axillary surgical intervention or axillary sentinel lymph node biopsy (SLNB). Patients with SLNB and pN+(sn) status will be secondly randomized to either SLNB alone or completion axillary lymph node dissection (ALND) in cases with less than four involved nodes (1-3 macrometastases). Patients with four or more metastatic sentinel lymph nodes should undergo completion ALND.

Postoperative systemic treatment should be based on local multidisciplinary tumor board recommendation according to the current German AGO and S3 guidelines. For women who are treated with breast-conserving surgery, the most common site of local recurrence is the conserved ipsilateral breast itself. Thus, whole-breast radiation therapy after breast-conserving surgery is mandatory and should be performed according to the current guidelines (S3, AGO, DEGRO).

During follow-up, patients will be assessed for disease recurrence according to standard clinical practice. History and physical examination will be performed every 6 months for the first 36 months and yearly thereafter. Annual mammography and sonography will be required; other testing will be based on symptoms and investigator preference. The total number of patients to be randomized into the trial will be approximately 7,095. An event-driven final efficacy analysis will be performed per-protocol for two primary objectives.

Study Type

Interventional

Enrollment (Actual)

5505

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Dornbirn, Austria, 6850
        • BGZ Dornbirn, Gynäkologie
      • Graz, Austria, 8036
        • LKH Uni-Klinikum Graz, Gynäkologie
      • Linz, Austria, 4020
        • Kepler Universitätsklinikum
      • Linz, Austria, 4010
        • Ordensklinikum-BHS
      • Salzburg, Austria, 5020
        • Universitätsfrauenklinik Salzburg
      • St. Veit/Glan, Austria, 9300
        • KH der Barmherzigen Brüder
      • Wien, Austria, 1140
        • Hanusch-Krankenhaus, Brustzentrum
      • Wolfsberg, Austria, 9400
        • Landes-Krankenhaus Wolfsberg, Chirurgie
  • Germany
    • BB
      • Brandenburg, BB, Germany, 14770
        • Städtisches Klinikum Brandenburg
      • Cottbus, BB, Germany, 03046
        • Carl-Thiem-Klinikum
      • Ludwigsfelde, BB, Germany, 14974
        • Ev. Krankenhaus, Frauenklinik
      • Potsdam, BB, Germany, 14467
        • Klinikum Ernst von Bergmann
    • BE
      • Berlin, BE, Germany, 10117
        • Charité Campus Mitte
      • Berlin, BE, Germany, 10365
        • Sana Klinikum Berlin-Lichtenberg
      • Berlin, BE, Germany, 10713
        • St. Gertrauden Krankenhaus
      • Berlin, BE, Germany, 12559
        • DRK Kliniken Köpenick
      • Berlin, BE, Germany, 13086
        • Park-Klinik Weißensee
      • Berlin, BE, Germany, 13589
        • Evang. Waldkrankenhaus Spandau
      • Berlin, BE, Germany, 14050
        • DRK-Kliniken Westend
      • Berlin, BE, Germany, 14163
        • Krankenhaus Waldfriede
      • Berlin-Buch, BE, Germany, 13125
        • Helios Klinikum, Klinik für Gynäkologie
    • BW
      • Aalen, BW, Germany, 73430
        • Ostalb-Klinikum, Brustzentrum Aalen
      • Bad Mergentheim, BW, Germany, 97980
        • Caritas-Krankenhaus Brustzentrum Tauberfranken
      • Baden-Baden, BW, Germany, 76532
        • Klinikum Mittelbach Brustzentrum
      • Biberach, BW, Germany, 88400
        • Sana-Klinikum Biberach
      • Bietigheim, BW, Germany, 74321
        • Krankenhaus Bietigheim
      • Bruchsal, BW, Germany, 76646
        • Fürst-Stirum-Klinik
      • Böblingen, BW, Germany, 71032
        • Klinikum Böblingen
      • Ehingen, BW, Germany, 89584
        • Brustzentrum Donau-Riß
      • Esslingen, BW, Germany, 73730
        • Klinikum Esslingen
      • Freiburg, BW, Germany, 79106
        • Universitätsklinikum Freiburg
      • Freudenstadt, BW, Germany, 72250
        • Frauenklinik Freudenstadt
      • Heidelberg, BW, Germany, 69120
        • Universitätsklinikum Heidelberg
      • Karlsruhe, BW, Germany, 76133
        • Städtisches Klinikum Karlsruhe
      • Karlsruhe, BW, Germany, 76199
        • ViDia Christliche Kliniken, Diakonissenkrankenhaus Karlsruhe
      • Ludwigsburg, BW, Germany, 71640
        • Klinikum Ludwigsburg
      • Lörrach, BW, Germany, 79539
        • St. Elisabethen Krankenhaus
      • Pforzheim, BW, Germany, 75175
        • Helios Klinik Pforzheim
      • Pforzheim, BW, Germany, 75179
        • Siloah St. Trudpert Klinikum
      • Reutlingen, BW, Germany, 72764
        • Klinikum am Steinenberg
      • Rottweil, BW, Germany, 78628
        • Helios Klinik Rottweil
      • Schorndorf, BW, Germany, 73614
        • Rems-Murr Klinik
      • Tuttlingen, BW, Germany, 78532
        • Klinikum Tuttlingen
      • Tübingen, BW, Germany, 72076
        • Universitätsfrauenklinik
      • Ulm, BW, Germany, 89075
        • Universitätsfrauenklinik Ulm
      • Villingen-Schwenningen, BW, Germany, 78050
        • Schwarzwald-Baar Klinikum
      • Winnenden, BW, Germany, 71364
        • Rems-Murr Kliniken
    • BY
      • Amberg, BY, Germany, 92224
        • Klinikum St. Marien
      • Ansbach, BY, Germany, 91522
        • AN regiomed Klinikum Ansbach
      • Aschaffenburg, BY, Germany, 63739
        • Klinikum Aschaffenburg
      • Augsburg, BY, Germany, 86150
        • Hämatologisch-Onkologische Praxis
      • Bayreuth, BY, Germany, 95445
        • Klinikum Bayreuth GmbH, Frauenklinik
      • Ebersberg, BY, Germany, 85560
        • Kreisklinik Ebersberg
      • Eggenfelden, BY, Germany, 84307
        • Gynäkologische Praxis
      • Fürth, BY, Germany, 90766
        • Klinikum Fürth
      • Kempten, BY, Germany, 87439
        • Klinikum Kempten-Oberallgau
      • Landshut, BY, Germany, 84034
        • Klinikum Landshut
      • Marktredwitz, BY, Germany, 95615
        • Klinikum Fichtelgebirge gGmbH, Brustzentrum
      • Memmingen, BY, Germany, 87700
        • Klinikum Memmingen
      • München, BY, Germany, 80337
        • Klinikum der Universität München
      • München, BY, Germany, 81545
        • Klinikum Harlaching, Frauenklinik
      • Passau, BY, Germany, 94032
        • Klinikum Passau
      • Regensburg, BY, Germany, 93053
        • Frauenklinik der Universität Regensburg, Caritas-Krankenhaus St. Josef
      • Starnberg, BY, Germany, 82319
        • Klinikum Starnberg
      • Traunstein, BY, Germany, 83278
        • Klinikum Traunstein
      • Weiden, BY, Germany, 92637
        • Kliniken Nordoberpfalz AG, Brustzentrum Weiden
      • Würzburg, BY, Germany, 97070
        • Rotkreuzklinik Würzburg
      • Würzburg, BY, Germany, 97074
        • Klinikum Mitte, Missio Brustzentrum
    • HB
      • Bremen, HB, Germany, 28209
        • St. Joseph Stift
      • Bremen, HB, Germany, 28239
        • DIAKO Krankenhaus Bremen
    • HE
      • Frankfurt, HE, Germany, 60431
        • Agaplesion Markus Krankenhaus
      • Frankfurt, HE, Germany, 60590
        • Universitätsklinikum Brustzentrum
      • Frankfurt am Main, HE, Germany, 65929
        • Klinikum Frankfurt Höchst
      • Gelnhausen, HE, Germany, 63571
        • Main-Kinzig-Kliniken Gelnhausen
      • Hanau, HE, Germany, 63450
        • Klinikum Hanau GmbH
      • Heppenheim, HE, Germany, 64646
        • Kreiskrankenhaus Bergstraße gGmbH
      • Kassel, HE, Germany, 34117
        • Elisabeth Krankenhaus Kassel
      • Kassel, HE, Germany, 34125
        • Klinikum Kassel
      • Offenbach, HE, Germany, 63069
        • Sana Klinikum Offenbach
      • Wiesbaden, HE, Germany, 65189
        • St. Josefs-Hospital, Frauenklinik
      • Wiesbaden, HE, Germany, 65197
        • Asklepios Paulinenklinik
      • Wiesbaden, HE, Germany, 65199
        • Helios Dr. Horst Schmidt Klinikum
    • HH
      • Hamburg, HH, Germany, 20246
        • Universitätsklinikum Hamburg, Brustzentrum
      • Hamburg, HH, Germany, 20259
        • Agaplesion Diakonieklinikum, Brustzentrum
      • Hamburg, HH, Germany, 21673
        • Gynäkologische Praxisklinik Harburg
      • Hamburg, HH, Germany, 22457
        • Albertinen-Krankenhaus, Brustzentrum
    • MV
      • Greifswald, MV, Germany, 17475
        • Universität Greifswald, Frauenklinik
      • Neubrandenburg, MV, Germany, 17036
        • Dietrich Bonhoeffer Klinikum, Brustzentrum
      • Rostock, MV, Germany, 18059
        • Universitäts-Frauenklinik
      • Schwerin, MV, Germany, 19049
        • HELIOS Kliniken Schwerin
    • NI
      • Celle, NI, Germany, 29223
        • AKH Celle, Brustzentrum
      • Georgsmarienhütte, NI, Germany, 49124
        • Franziskus Hospital Harderberg
      • Gifhorn, NI, Germany, 38518
        • Helios Klinikum Gifhorn
      • Hannover, NI, Germany, 30559
        • Henriettenstiftung Frauenklinik
      • Hannover, NI, Germany, 30559
        • Vinzenzkrankenhaus Hannover
      • Hannover, NI, Germany, 30625
        • MHH Frauenklinik
      • Hildesheim, NI, Germany, 31134
        • St. Bernward Krankenhaus
      • Lingen, NI, Germany, 49808
        • Bonifatius-Hospital, Brustzentrum
      • Nordhorn, NI, Germany, 48527
        • Euregio-Klinik Brustzentrum Nordhorn
      • Obernkirchen, NI, Germany, 31683
        • Agaplesion Ev. Klinikum, Brustzentrum Schaumburg
      • Osnabrück, NI, Germany, 49076
        • Klinikum Osnabruck
      • Rotenburg, NI, Germany, 27356
        • Diakoniekrankenhaus, Frauenklinik
      • Wolfsburg, NI, Germany, 38440
        • Klinikum Wolfsburg, Frauenklinik
    • Nordrhein
      • Bochum, Nordrhein, Germany, 44791
        • Augusta-Klinik
      • Bonn, Nordrhein, Germany, 53105
        • Universitätsfrauenklinik Bonn
      • Bottrop, Nordrhein, Germany, 46236
        • Marienhospital Bottrop
      • Düsseldorf, Nordrhein, Germany, 40225
        • Frauenklinik der H.-Heine-Universität
      • Essen, Nordrhein, Germany, 45122
        • Universitätsklinikum Essen Frauenklinik
      • Essen, Nordrhein, Germany, 45136
        • Kliniken Essen-Mitte
      • Köln, Nordrhein, Germany, 50931
        • Uniklinik Köln
      • Köln, Nordrhein, Germany, 50935
        • St. Elisabeth Krankenhaus, Brustzentrum
      • Lüdenscheid, Nordrhein, Germany, 58515
        • Klinikum Märkische Kliniken, Brustzentrum
      • Lünen, Nordrhein, Germany, 44534
        • Klinikum Lünen, Brustzentrum
      • Münster, Nordrhein, Germany, 48145
        • St. Franziskus-Hospital
      • Münster, Nordrhein, Germany, 48149
        • Universitatsklinikum Munster
      • Schwerte, Nordrhein, Germany, 58239
        • Marienkrankenhaus
      • Siegen, Nordrhein, Germany, 57072
        • St. Marienkrankenhaus, Frauenklinik
      • Troisdorf, Nordrhein, Germany, 53840
        • St. Josef-Hospital, BZ Rhein-Sieg
      • Unna, Nordrhein, Germany, 59423
        • Katharinen-Hospital, Brustzentrum
      • Wesel, Nordrhein, Germany, 46483
        • Marien-Hospital
    • RP
      • Kaiserslautern, RP, Germany, 67655
        • Westpfalz Klinikum
      • Koblenz, RP, Germany, 56073
        • BZ Mittelrhein Koblenz+Mayen
      • Ludwigshafen, RP, Germany, 67063
        • Klinikum Ludwigshafen
      • Speyer, RP, Germany, 67346
        • Diakonissen-Stiftungs-Krankenhaus Speyer
      • Worms, RP, Germany, 67550
        • Stadtkrankenhaus Worms
    • SH
      • Eutin, SH, Germany, 23701
        • Sana-Klinik
      • Flensburg, SH, Germany, 24939
        • DIAKO Diakonissenkrankenhaus
      • Kiel, SH, Germany, 24105
        • Universitatsklinikum Schleswig-Hostein
      • Lübeck, SH, Germany, 23538
        • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
    • SN
      • Borna, SN, Germany, 04552
        • Brustzentrum Nordsachsen
      • Dresden, SN, Germany, 01099
        • Diakonissenkrankenhaus
      • Dresden, SN, Germany, 01307
        • Krankenhaus St. Joseph-Stift
      • Dresden, SN, Germany, 01307
        • Universität Dresden, Frauenklinik
      • Görlitz, SN, Germany, 02828
        • Städtisches Klinikum
      • Leipzig, SN, Germany, 04103
        • Universitätsklinikum Leipzig, Brustzentrum
      • Leipzig, SN, Germany, 04277
        • St. Elisabeth Krankenhaus
      • Rodewisch, SN, Germany, 08228
        • Klinikum Obergöltzsch Rodewisch
      • Schkeuditz, SN, Germany, 04435
        • Helios Klinik
    • Saint
      • Halle, Saint, Germany, 06110
        • Krankenhaus St. Elisabeth und St. Barbara
      • Halle/Saale, Saint, Germany, 06120
        • Universität Halle/Saale, Frauenklinik
      • Magdeburg, Saint, Germany, 39110
        • Klinik St. Marienstift
      • Salzwedel, Saint, Germany, 29410
        • Altmark-Klinikum Brustzentrum
      • Stendal, Saint, Germany, 39576
        • Johanniter-Krankenhaus, Frauenklinik
      • Wernigerode, Saint, Germany, 38855
        • Harzklinikum, Brustzentrum Harz
    • TH
      • Bad Langensalza, TH, Germany, 99947
        • Hufeland-Klinik Bad Langensalza
      • Gera, TH, Germany, 07548
        • SRH Waldklinikum
      • Jena, TH, Germany, 07747
        • Universitatsklinikum Jena
      • Meiningen, TH, Germany, 98617
        • Helios Klinikum Meiningen, Brustzentrum
      • Suhl, TH, Germany, 98527
        • SRH Zentralklinikum Suhl
      • Sömmerda, TH, Germany, 99610
        • DRK Krankenhaus, Brustzentrum

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Written informed consent prior to beginning breast-conserving surgery, including expected cooperation of the patients for follow-up, must be obtained and documented according to the local regulatory requirements
  • Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy or open biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is planned
  • Age at diagnosis at least 18 years
  • Preoperative imaging techniques with estimated tumor size of <5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status)
  • Clinically and sonographically tumor-free axilla prior to core biopsy (cN0/iN0)
  • In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration (FNA) biopsy of the sonographically suspected lymph node is required before randomization
  • No clinical evidence for distant metastasis (M0)
  • Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation)

Exclusion Criteria:

  • History of malignancy within last 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix
  • Time since core biopsy >3 months (optimal <1 month)
  • Previous and already (neoadjuvant) treated invasive breast carcinoma
  • Histologically non-invasive breast carcinoma
  • cT3/T4 or iT3/T4 tumors
  • pregnant or lactating patients
  • Planned total mastectomy (e.g. multicentric tumors )
  • Planned intraoperative radiotherapy (e.g. Intrabeam) or postoperative partial breast irradiation (e.g. multicatheter technique) alone; both procedures are allowed as boost techniques
  • Male patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: no axillary surgery
Procedure: no axillary surgery versus SLNB
in cases with newly diagnosed breast cancer and clinically negative axillary status
Active Comparator: sentinel lymph node biopsy
standard arm in first randomization
Procedure: no axillary surgery versus SLNB
in cases with newly diagnosed breast cancer and clinically negative axillary status
Experimental: sentinel lymph node biopsy alone
Procedure: SLNB versus completion ALND
in cases with 1-3 macrometastases in sentinel lymph nodes
Active Comparator: completion axillary lymph node dissection
standard arm in second randomization
Procedure: SLNB versus completion ALND
in cases with 1-3 macrometastases in sentinel lymph nodes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
invasive disease-free survival (IDFS) after breast-conserving surgery
Time Frame: 5 years
non-inferiority question
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rostock

Collaborators

German Breast Group
German Cancer Aid

Investigators

  • Study Chair: Toralf Reimer, MD, PhD, University Medicine Rostock

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2015

Primary Completion (Anticipated)

September 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

June 4, 2015

First Submitted That Met QC Criteria

June 4, 2015

First Posted (Estimate)

June 9, 2015

Study Record Updates

Last Update Posted (Actual)

December 21, 2022

Last Update Submitted That Met QC Criteria

December 16, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GBG 75 / ABCSG 43

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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