Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery

Breast Cancer Clinical Trial

— INSEMA  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02466737
• Other study ID #: GBG 75 / ABCSG 43
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 2015
• Est. completion date: December 2024

Study information

• Verified date: December 2022
• Source: University of Rostock
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 5505
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• no axillary surgery versus SLNB
in cases with newly diagnosed breast cancer and clinically negative axillary status
• SLNB versus completion ALND
in cases with 1-3 macrometastases in sentinel lymph nodes

Locations

Country	Name	City	State
Austria	BGZ Dornbirn, Gynäkologie	Dornbirn
Austria	LKH Uni-Klinikum Graz, Gynäkologie	Graz
Austria	Kepler Universitätsklinikum	Linz
Austria	Ordensklinikum-BHS	Linz
Austria	Universitätsfrauenklinik Salzburg	Salzburg
Austria	KH der Barmherzigen Brüder	St. Veit/Glan
Austria	Hanusch-Krankenhaus, Brustzentrum	Wien
Austria	Landes-Krankenhaus Wolfsberg, Chirurgie	Wolfsberg
Germany	Ostalb-Klinikum, Brustzentrum Aalen	Aalen	BW
Germany	Klinikum St. Marien	Amberg	BY
Germany	AN regiomed Klinikum Ansbach	Ansbach	BY
Germany	Klinikum Aschaffenburg	Aschaffenburg	BY
Germany	Hämatologisch-onkologische Praxis	Augsburg	BY
Germany	Hufeland-Klinik Bad Langensalza	Bad Langensalza	TH
Germany	Caritas-Krankenhaus Brustzentrum Tauberfranken	Bad Mergentheim	BW
Germany	Klinikum Mittelbach Brustzentrum	Baden-Baden	BW
Germany	Klinikum Bayreuth GmbH, Frauenklinik	Bayreuth	BY
Germany	Charite Campus Mitte	Berlin	BE
Germany	DRK Kliniken Köpenick	Berlin	BE
Germany	DRK-Kliniken Westend	Berlin	BE
Germany	Evang. Waldkrankenhaus Spandau	Berlin	BE
Germany	Krankenhaus Waldfriede	Berlin	BE
Germany	Park-Klinik Weißensee	Berlin	BE
Germany	Sana Klinikum Berlin-Lichtenberg	Berlin	BE
Germany	St. Gertrauden Krankenhaus	Berlin	BE
Germany	Helios Klinikum, Klinik für Gynäkologie	Berlin-Buch	BE
Germany	Sana-Klinikum Biberach	Biberach	BW
Germany	Krankenhaus Bietigheim	Bietigheim	BW
Germany	Klinikum Böblingen	Böblingen	BW
Germany	Augusta-Klinik	Bochum	Nordrhein
Germany	Universitätsfrauenklinik Bonn	Bonn	Nordrhein
Germany	Brustzentrum Nordsachsen	Borna	SN
Germany	Marienhospital Bottrop	Bottrop	Nordrhein
Germany	Städtisches Klinikum Brandenburg	Brandenburg	BB
Germany	DIAKO Krankenhaus Bremen	Bremen	HB
Germany	St. Joseph Stift	Bremen	HB
Germany	Fürst-Stirum-Klinik	Bruchsal	BW
Germany	AKH Celle, Brustzentrum	Celle	NI
Germany	Carl-Thiem-Klinikum	Cottbus	BB
Germany	Diakonissenkrankenhaus	Dresden	SN
Germany	Krankenhaus St. Joseph-Stift	Dresden	SN
Germany	Universität Dresden, Frauenklinik	Dresden	SN
Germany	Frauenklinik der H.-Heine-Universität	Düsseldorf	Nordrhein
Germany	Kreisklinik Ebersberg	Ebersberg	BY
Germany	Gynäkologische Praxis	Eggenfelden	BY
Germany	Brustzentrum Donau-Riß	Ehingen	BW
Germany	Kliniken Essen-Mitte	Essen	Nordrhein
Germany	Universitätsklinikum Essen Frauenklinik	Essen	Nordrhein
Germany	Klinikum Esslingen	Esslingen	BW
Germany	Sana-Klinik	Eutin	SH
Germany	DIAKO Diakonissenkrankenhaus	Flensburg	SH
Germany	Agaplesion Markus Krankenhaus	Frankfurt	HE
Germany	Universitätsklinikum Brustzentrum	Frankfurt	HE
Germany	Klinikum Frankfurt Höchst	Frankfurt am Main	HE
Germany	Universitätsklinikum Freiburg	Freiburg	BW
Germany	Frauenklinik Freudenstadt	Freudenstadt	BW
Germany	Klinikum Fürth	Fürth	BY
Germany	Main-Kinzig-Kliniken Gelnhausen	Gelnhausen	HE
Germany	Franziskus Hospital Harderberg	Georgsmarienhütte	NI
Germany	SRH Waldklinikum	Gera	TH
Germany	Helios Klinikum Gifhorn	Gifhorn	NI
Germany	Städtisches Klinikum	Görlitz	SN
Germany	Universität Greifswald, Frauenklinik	Greifswald	MV
Germany	Krankenhaus St. Elisabeth und St. Barbara	Halle	Saint
Germany	Universität Halle/Saale, Frauenklinik	Halle/Saale	Saint
Germany	Agaplesion Diakonieklinikum, Brustzentrum	Hamburg	HH
Germany	Albertinen-Krankenhaus, Brustzentrum	Hamburg	HH
Germany	Gynäkologische Praxisklinik Harburg	Hamburg	HH
Germany	Universitätsklinikum Hamburg, Brustzentrum	Hamburg	HH
Germany	Klinikum Hanau GmbH	Hanau	HE
Germany	Henriettenstiftung Frauenklinik	Hannover	NI
Germany	MHH Frauenklinik	Hannover	NI
Germany	Vinzenzkrankenhaus Hannover	Hannover	NI
Germany	Universitätsklinikum Heidelberg	Heidelberg	BW
Germany	Kreiskrankenhaus Bergstraße gGmbH	Heppenheim	HE
Germany	St. Bernward Krankenhaus	Hildesheim	NI
Germany	Universitätsklinikum Jena	Jena	TH
Germany	Westpfalz Klinikum	Kaiserslautern	RP
Germany	Städtisches Klinikum Karlsruhe	Karlsruhe	BW
Germany	ViDia Christliche Kliniken, Diakonissenkrankenhaus Karlsruhe	Karlsruhe	BW
Germany	Elisabeth Krankenhaus Kassel	Kassel	HE
Germany	Klinikum Kassel	Kassel	HE
Germany	Klinikum Kempten-Oberallgäu	Kempten	BY
Germany	Universitätsklinikum Schleswig-Hostein	Kiel	SH
Germany	BZ Mittelrhein Koblenz+Mayen	Koblenz	RP
Germany	St. Elisabeth Krankenhaus, Brustzentrum	Köln	Nordrhein
Germany	Uniklinik Köln	Köln	Nordrhein
Germany	Klinikum Landshut	Landshut	BY
Germany	St. Elisabeth Krankenhaus	Leipzig	SN
Germany	Universitätsklinikum Leipzig, Brustzentrum	Leipzig	SN
Germany	Bonifatius-Hospital, Brustzentrum	Lingen	NI
Germany	St. Elisabethen Krankenhaus	Lörrach	BW
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck	SH
Germany	Klinikum Märkische Kliniken, Brustzentrum	Lüdenscheid	Nordrhein
Germany	Klinikum Ludwigsburg	Ludwigsburg	BW
Germany	Ev. Krankenhaus, Frauenklinik	Ludwigsfelde	BB
Germany	Klinikum Ludwigshafen	Ludwigshafen	RP
Germany	Klinikum Lünen, Brustzentrum	Lünen	Nordrhein
Germany	Klinik St. Marienstift	Magdeburg	Saint
Germany	Klinikum Fichtelgebirge gGmbH, Brustzentrum	Marktredwitz	BY
Germany	Helios Klinikum Meiningen, Brustzentrum	Meiningen	TH
Germany	Klinikum Memmingen	Memmingen	BY
Germany	Klinikum der Universität München	München	BY
Germany	Klinikum Harlaching, Frauenklinik	München	BY
Germany	St. Franziskus-Hospital	Münster	Nordrhein
Germany	Universitätsklinikum Münster	Münster	Nordrhein
Germany	Dietrich Bonhoeffer Klinikum, Brustzentrum	Neubrandenburg	MV
Germany	Euregio-Klinik Brustzentrum Nordhorn	Nordhorn	NI
Germany	Agaplesion Ev. Klinikum, Brustzentrum Schaumburg	Obernkirchen	NI
Germany	Sana Klinikum Offenbach	Offenbach	HE
Germany	Klinikum Osnabrück	Osnabrück	NI
Germany	Klinikum Passau	Passau	BY
Germany	Helios Klinik Pforzheim	Pforzheim	BW
Germany	Siloah St. Trudpert Klinikum	Pforzheim	BW
Germany	Klinikum Ernst von Bergmann	Potsdam	BB
Germany	Frauenklinik der Universität Regensburg, Caritas-Krankenhaus St. Josef	Regensburg	BY
Germany	Klinikum am Steinenberg	Reutlingen	BW
Germany	Klinikum Obergöltzsch Rodewisch	Rodewisch	SN
Germany	Universitäts-Frauenklinik	Rostock	MV
Germany	Diakoniekrankenhaus, Frauenklinik	Rotenburg	NI
Germany	Helios Klinik Rottweil	Rottweil	BW
Germany	Altmark-Klinikum Brustzentrum	Salzwedel	Saint
Germany	Helios Klinik	Schkeuditz	SN
Germany	Rems-Murr Klinik	Schorndorf	BW
Germany	Helios Kliniken Schwerin	Schwerin	MV
Germany	Marienkrankenhaus	Schwerte	Nordrhein
Germany	St. Marienkrankenhaus, Frauenklinik	Siegen	Nordrhein
Germany	DRK Krankenhaus, Brustzentrum	Sömmerda	TH
Germany	Diakonissen-Stiftungs-Krankenhaus Speyer	Speyer	RP
Germany	Klinikum Starnberg	Starnberg	BY
Germany	Johanniter-Krankenhaus, Frauenklinik	Stendal	Saint
Germany	SRH Zentralklinikum Suhl	Suhl	TH
Germany	Klinikum Traunstein	Traunstein	BY
Germany	St. Josef-Hospital, BZ Rhein-Sieg	Troisdorf	Nordrhein
Germany	Universitätsfrauenklinik	Tübingen	BW
Germany	Klinikum Tuttlingen	Tuttlingen	BW
Germany	Universitätsfrauenklinik Ulm	Ulm	BW
Germany	Katharinen-Hospital, Brustzentrum	Unna	Nordrhein
Germany	Schwarzwald-Baar Klinikum	Villingen-Schwenningen	BW
Germany	Kliniken Nordoberpfalz AG, Brustzentrum Weiden	Weiden	BY
Germany	Harzklinikum, Brustzentrum Harz	Wernigerode	Saint
Germany	Marien-Hospital	Wesel	Nordrhein
Germany	Asklepios Paulinenklinik	Wiesbaden	HE
Germany	Helios Dr. Horst Schmidt Klinikum	Wiesbaden	HE
Germany	St. Josefs-Hospital, Frauenklinik	Wiesbaden	HE
Germany	Rems-Murr Kliniken	Winnenden	BW
Germany	Klinikum Wolfsburg, Frauenklinik	Wolfsburg	NI
Germany	Stadtkrankenhaus Worms	Worms	RP
Germany	Klinikum Mitte, Missio Brustzentrum	Würzburg	BY
Germany	Rotkreuzklinik Würzburg	Würzburg	BY

Sponsors (3)

Lead Sponsor	Collaborator
University of Rostock	German Breast Group, German Cancer Aid

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (3)

Hildebrandt G, Stachs A, Gerber B, Potenberg J, Krug D, Wolter K, Kuhn T, Zierhut D, Sedlmayer F, Kaiser J, Reitsamer R, Heil J, Nekljudova V, Bekes I, Loibl S, Reimer T. Central Review of Radiation Therapy Planning Among Patients with Breast-Conserving S — View Citation

Reimer T, Stachs A, Nekljudova V, Loibl S, Hartmann S, Wolter K, Hildebrandt G, Gerber B. Restricted Axillary Staging in Clinically and Sonographically Node-Negative Early Invasive Breast Cancer (c/iT1-2) in the Context of Breast Conserving Therapy: First — View Citation

Reimer T, Stachs A, Veselinovic K, Polata S, Muller T, Kuhn T, Heil J, Ataseven B, Reitsamer R, Hildebrandt G, Knauer M, Golatta M, Stefek A, Zahm DM, Thill M, Nekljudova V, Krug D, Loibl S, Gerber B; INSEMA investigators. Patient-reported outcomes for th — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	invasive disease-free survival (IDFS) after breast-conserving surgery	non-inferiority question	5 years