Efficacy Study of Herceptin to Treat HER2-negative CTC Breast Cancer

NCT ID: NCT01548677

Last Updated: 2019-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 1317 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2017-03-31

Brief Summary

This is a randomized phase II trial for patients with HER2 negative primary Breast Cancer (BC) who after completing (neo) adjuvant chemotherapy and surgery have detectable circulating tumour cells (CTC) in peripheral blood.

Eligible patients will be randomised in 1:1 ratio to either the trastuzumab arm or the observation arm.

Detailed Description

This is a randomized phase II trial for patients with HER2 negative primary BC who after completing (neo) adjuvant chemotherapy and surgery have detectable CTC(s) in peripheral blood (see eligibility criteria for details). Eligible patients will be randomized in 1:1 ratio to either the trastuzumab arm or the observation arm. Patients randomized to the trastuzumab arm will receive a total of 6 intravenous (IV) administrations every 3 weeks (loading dose 8 mg/kg IV and 5 cycles at 6 mg/kg every 3 weeks). Patients randomized to observation arm shall be observed for 18 weeks. Left ventricular ejection fraction (LVEF) assessment (MUGA and/or ECHO) will be done at baseline for all patients to be randomized. The next LVEF assessments of weeks 9 and week 18 will be done only in patients randomized to trastuzumab arm. Patient registered but with CTC negative result will not be followed-up.

Conditions

Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Circulating Tumor Cells

Study Design

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

Study Groups

observation

18 weeks

Group Type: NO_INTERVENTION

No interventions assigned to this group

Herceptin (trastuzumab)

18 weeks

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: DRUG

8 mg/kg of loading dose IV over 90 minutes for the first cycle, followed by 6 mg/kg IV over 60 minutes every 3 weeks for the 5 subsequent cycles.

Interventions

trastuzumab

8 mg/kg of loading dose IV over 90 minutes for the first cycle, followed by 6 mg/kg IV over 60 minutes every 3 weeks for the 5 subsequent cycles.

Intervention Type: DRUG

Other Intervention Names

endocrine therapy; anti HER2 therapy

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Written informed consent must be given according to ICH/GCP, and national/local regulations
• Availability of peripheral blood draw for CTC blood test
• Tumor block or minimum 10 unstained slides of 4 μm of primary tumor must be available prior to registration for centralized HER2 testing
• ER status available
• Adequately excised non-metastatic and non-relapsed operable primary invasive HER2-negative adeno-carcinoma of the breast *:
• the patient should have completed either
• adjuvant chemotherapy or
• neoadjuvant chemotherapy; in this case residual invasive disease in breast or lymph nodes is required (no complete pathological response) no further adjuvant chemotherapy treatment planned. Prior chemotherapy with doxorubicin restricted to a total dose of 360 mg/m2 or with epirubicin restricted to a total dose of 720 mg/m2 is allowed
• No prior use of anti-HER2 therapy for any reason or immunotherapy for BC
• No concomitant use of bisphosphonate therapy or denosumab for any reason. Prior use of these agents is allowed provided that last treatment has been received at least 4 weeks before registration in the study
• No prior mediastinal irradiation except internal mammary node irradiation for the present BC
• Concomitant adjuvant hormonal therapy or radiotherapy (if applicable) is allowed upon physician's choice
• The interval between definitive surgery (neoadjuvant population) or end of adjuvant chemotherapy (adjuvant population) and registration must be at least 3 weeks but no more than 24 weeks
• No evidence of unresolved or unstable toxicity from prior surgery, adjuvant chemotherapy or radiotherapy
• No history of prior invasive breast carcinoma, except for the BC diagnosed and treated before entry. Unifocal or multifocal unilateral (one breast) or unifocal or multifocal synchronous bilateral breast (both breasts) cancer are acceptable if all invasive tumor foci are HER2- negative. History of previous ductal carcinoma in situ is allowed
• No history of any malignant neoplasms in the past 5 years except for curatively treated basal and squamous cell carcinoma of the skin
• No prior autologous or allogeneic stem cell transplantation
• No history of serious cardiac illness or medical conditions, including but not confined to:
• History of documented congestive heart failure
• High risk uncontrolled arrhythmias
• Angina pectoris requiring anti-anginal medication
• Clinically significant valvular heart disease
• Evidence of transmural infarction on ECG
• Poorly controlled hypertension (e.g. systolic > 180 mm Hg or diastolic > 100 mm Hg)
• No history of other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration
• WHO performance status 0-1
• No concurrent participation in another trial
• No clinically significant active infections

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

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Janssen Diagnostics, LLC

INDUSTRY

Sponsor Role: collaborator

SUCCESS

UNKNOWN

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michail Ignatiadis, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Jules Bordet, Brussels, Belgium

Martine Piccart, MD

Role: STUDY_CHAIR

Institut Jules Bordet, Brussels, Belgium

Christos Sotiriou, MD

Role: STUDY_CHAIR

Institut Jules Bordet, Brussels, Belgium

Jean-Yves Pierga, MD

Role: STUDY_CHAIR

Institut Curie, Paris, France

Brigitte Rack, MD

Role: STUDY_CHAIR

Ludwig-Maximilians-Universitaet Muenchen - Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe - Innenstadt, Munich, Germany

Locations

Onze Lieve Vrouw Ziekenhuis

Aalst, , Belgium

Hopital Universitaire Brugmann

Brussels, , Belgium

Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme

Brussels, , Belgium

Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet

Brussels, , Belgium

Hopital De Jolimont

Haine-Saint-Paul, , Belgium

U.Z. Leuven - Campus Gasthuisberg

Leuven, , Belgium

C.H.U. Sart-Tilman

Liège, , Belgium

Clinique et Maternité Sainte Elisabeth

Namur, , Belgium

AZ Damiaan

Ostend, , Belgium

Institut Bergonie

Bordeaux, , France

CHU de Brest

Brest, , France

Centre Regional Francois Baclesse

Caen, , France

Centre Hospitalier Alpes Léman

Contamine-sur-Arve, , France

Centre Hospitalier de la Dracénie

Draguignan, , France

CHU de Grenoble - La Tronche - Hôpital A. Michallon

Grenoble, , France

Centre Hospitalier Departemental Vendée

La Roche-sur-Yon, , France

Centre Hospitalier de Versailles - Hopital Andre Mignot

Le Chesnay, , France

CHU de Limoges - Hopital Dupuytren

Limoges, , France

Clinique de la Sauvegarde

Lyon, , France

Centre Hospitalier D'Annecy

Metz-Tessy, , France

Centre Hospitalier de Mont-de-Marsan

Mont-de-Marsan, , France

Centre Catherine De Sienne

Nantes, , France

Institut Curie

Paris, , France

Institut Curie - Hopital Rene Huguenin

Saint-Cloud, , France

Hopitaux Universitaires de Strasbourg - Hôpitaux Universitaires de Strasbourg - Hôpital civil

Strasbourg, , France

Hopitaux du Leman - Site Georges Pianta

Thonon-les-Bains, , France

CH de Valence

Valence, , France

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Gustave Roussy

Villejuif, , France

Klinikum St. Marien

Amberg, , Germany

Gemeinschaftspraxis Augsburg

Augsburg, , Germany

Klinikum Augsburg

Augsburg, , Germany

Praxisklinik Krebsheilkunde für Frauen

Berlin, , Germany

Medizinischen Zentrum Bonn

Bonn, , Germany

Marienhospital Bottrop gGmbH

Bottrop, , Germany

Klinikum Sindelfingen-Boeblingen

Böblingen, , Germany

Gemeinschaftspraxis Lorenz / Hecker / Wesche

Braunschweig, , Germany

Onkologische-Hämatologischen Schwerpunktpraxis

Bremen, , Germany

Universitaetsklinikum Koeln

Cologne, , Germany

Onkologische Gemeinschaftspraxis

Dresden, , Germany

Universitaetsklinikum Carl Gustav Carus

Dresden, , Germany

Luisenkrankenhaus GmbH & Co. KG

Düsseldorf, , Germany

Universitaetsklinik Duesseldorf

Düsseldorf, , Germany

Universitaetsklinik Erlangen

Erlangen, , Germany

Universitaetsklinikum - Essen

Essen, , Germany

Staedtische Kliniken

Esslingen am Neckar, , Germany

Ev.-Luth. Diakonissenanstalt Flensburg

Flensburg, , Germany

Staedtische Kliniken Frankfurt Am Main-Hoechst

Frankfurt am Main, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitaets-Krankenhaus Eppendorf

Hamburg, , Germany

Gynäkologisch-Onkologischen Schwerpunktpraxis

Hanover, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Gemeinschaftspraxis Dr. Pourfard / Dr. Uleer

Hildesheim, , Germany

St. Marien-Klinik GmbH Frauenklinik der St. Vincentius-Kliniken gAG

Karlsruhe, , Germany

Universitaetsklinikum Schleswig-Holstein - Campus Kiel

Kiel, , Germany

Klinikum Landshut

Landshut, , Germany

Staedtisches Klinikum Leipzig - Klinikum St. Georg gGmbH

Leipzig, , Germany

Klinikum Ludwigsburg

Ludwigsburg, , Germany

Gemeinschaftspraxis Dr. Goldmann/ Dr. Ebert

Lüneburg, , Germany

UniversitaetsMedizin Mannheim

Mannheim, , Germany

Klinikum Schwaebisch-Gmuend

Mutlangen, , Germany

Gemeinschaftspraxis Prof. Salat / Dr. Stötzer

München, , Germany

Ludwig-Maximilians-Universitaet Muenchen - Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe - Innenstadt

München, , Germany

Muencher Onkol. Praxis Elisenhof

München, , Germany

Onkologische Praxis Oldenburg

Oldenburg, , Germany

Studienzentrum Onkologie Ravensburg

Ravensburg, , Germany

RoMed Klinikum Rosenheim

Rosenheim, , Germany

HELIOS Kliniken - HELIOS Klinik Rottweil

Rottweil, , Germany

HELIOS Kliniken - HELIOS Brustzentrums Nordachsen - HELIOS Klinik Schkeuditz

Schkeuditz, , Germany

Diakonie-Klinikum Schwäbisch Hall gGmbH

Schwäbisch Hall, , Germany

Leopoldina-Krankenhaus der Stadt Schweinfurt gGmbH

Schweinfurt, , Germany

Kliniken Landkreis Sigmaringen GmbH

Sigmaringen, , Germany

Klinikum Stuttgart

Stuttgart, , Germany

Klinikum Traunstein

Traunstein, , Germany

Gesellschaft für onkologische Studien, Praxismanagement und -Logistik

Troisdorf, , Germany

Eberhard Karls Universitaet Tuebingen - Universitaetsfrauenklinik Tuebingen

Tübingen, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

Gesundheitszentren Rhein-Neckar - GRN-Klinik Weinheim

Weinheim, , Germany

Onkologische Schwerpunktpraxis Wupperta

Wuppertal, , Germany

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, , United Kingdom

Countries

Belgium; France; Germany; United Kingdom

References

Ignatiadis M, Rack B, Rothe F, Riethdorf S, Decraene C, Bonnefoi H, Dittrich C, Messina C, Beauvois M, Trapp E, Goulioti T, Tryfonidis K, Pantel K, Repollet M, Janni W, Piccart M, Sotiriou C, Litiere S, Pierga JY. Liquid biopsy-based clinical research in early breast cancer: The EORTC 90091-10093 Treat CTC trial. Eur J Cancer. 2016 Aug;63:97-104. doi: 10.1016/j.ejca.2016.04.024. Epub 2016 Jun 10.

Reference Type: DERIVED

PMID: 27289552 (View on PubMed)

Related Links

http://www.eortc.be/clinicaltrials/details.asp?protocol=90091

Related Info

Other Identifiers

2009-017485-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-90091-10093

Identifier Type: -

Identifier Source: org_study_id