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

NCT01548677 | Completed Phase 2 DMC

• 2 other identifiers: EORTC-90091-100932009-017485-23
• Study Type: interventional
• Target: 1,317
• Locations: 4 countries
• Sites: 80

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.

Conditions

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

Keywords

Circulating Tumour Cells; HER2 negative primary breast cancer; HER2 positive CTC; Trastuzumab

Outcome Measures

Primary Outcomes (1)

• CTC detection

  To compare circulating tumour cell (CTC)detection rate at week 18 between trastuzumab treatment arm and observational arm.

  18 weeks post randomisation

Secondary Outcomes (7)

• RFI (recurrence free interval)

  2 years after LPI (last patient in)

• IDFS (Invasive Disease Free Survival)

  2 years after LPI

• DFS (disease free survival)

  2 years after LPI

• OS (overall survival)

  2 years after LPI

• CTC essay

  2 years after LPI

Study Arms (2)

observation

NO INTERVENTION

18 weeks

Herceptin (trastuzumab)

EXPERIMENTAL

18 weeks

Drug: trastuzumab

Interventions

trastuzumab 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.

Also known as: endocrine therapy, anti HER2 therapy

Herceptin (trastuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

* 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Hoffmann-La Roche: collaborator
• Janssen Diagnostics, LLC: collaborator
• SUCCESS: collaborator
• UNICANCER: collaborator

Study Sites (80)

Onze Lieve Vrouw Ziekenhuis

Aalst, Belgium

Location

Hopital Universitaire Brugmann

Brussels, Belgium

Location

Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme

Brussels, Belgium

Location

Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet

Brussels, Belgium

Location

Hopital De Jolimont

Haine-Saint-Paul, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, Belgium

Location

C.H.U. Sart-Tilman

Liège, Belgium

Location

Clinique et Maternité Sainte Elisabeth

Namur, Belgium

Location

AZ Damiaan

Ostend, Belgium

Location

Institut Bergonie

Bordeaux, France

Location

CHU de Brest

Brest, France

Location

Centre Regional Francois Baclesse

Caen, France

Location

Centre Hospitalier Alpes Léman

Contamine-sur-Arve, France

Location

Centre Hospitalier de la Dracénie

Draguignan, France

Location

CHU de Grenoble - La Tronche - Hôpital A. Michallon

Grenoble, France

Location

Centre Hospitalier Departemental Vendée

La Roche-sur-Yon, France

Location

Centre Hospitalier de Versailles - Hopital Andre Mignot

Le Chesnay, France

Location

CHU de Limoges - Hopital Dupuytren

Limoges, France

Location

Clinique de la Sauvegarde

Lyon, France

Location

Centre Hospitalier D'Annecy

Metz-Tessy, France

Location

Centre Hospitalier de Mont-de-Marsan

Mont-de-Marsan, France

Location

Centre Catherine De Sienne

Nantes, France

Location

Institut Curie

Paris, France

Location

Institut Curie - Hopital Rene Huguenin

Saint-Cloud, France

Location

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

Strasbourg, France

Location

Hopitaux du Leman - Site Georges Pianta

Thonon-les-Bains, France

Location

CH de Valence

Valence, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy

Villejuif, France

Location

Klinikum St. Marien

Amberg, Germany

Location

Gemeinschaftspraxis Augsburg

Augsburg, Germany

Location

Klinikum Augsburg

Augsburg, Germany

Location

Praxisklinik Krebsheilkunde für Frauen

Berlin, Germany

Location

Medizinischen Zentrum Bonn

Bonn, Germany

Location

Marienhospital Bottrop gGmbH

Bottrop, Germany

Location

Klinikum Sindelfingen-Boeblingen

Böblingen, Germany

Location

Gemeinschaftspraxis Lorenz / Hecker / Wesche

Braunschweig, Germany

Location

Onkologische-Hämatologischen Schwerpunktpraxis

Bremen, Germany

Location

Universitaetsklinikum Koeln

Cologne, Germany

Location

Onkologische Gemeinschaftspraxis

Dresden, Germany

Location

Universitaetsklinikum Carl Gustav Carus

Dresden, Germany

Location

Luisenkrankenhaus GmbH & Co. KG

Düsseldorf, Germany

Location

Universitaetsklinik Duesseldorf

Düsseldorf, Germany

Location

Universitaetsklinik Erlangen

Erlangen, Germany

Location

Universitaetsklinikum - Essen

Essen, Germany

Location

Staedtische Kliniken

Esslingen am Neckar, Germany

Location

Ev.-Luth. Diakonissenanstalt Flensburg

Flensburg, Germany

Location

Staedtische Kliniken Frankfurt Am Main-Hoechst

Frankfurt am Main, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Universitaets-Krankenhaus Eppendorf

Hamburg, Germany

Location

Gynäkologisch-Onkologischen Schwerpunktpraxis

Hanover, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Gemeinschaftspraxis Dr. Pourfard / Dr. Uleer

Hildesheim, Germany

Location

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

Karlsruhe, Germany

Location

Universitaetsklinikum Schleswig-Holstein - Campus Kiel

Kiel, Germany

Location

Klinikum Landshut

Landshut, Germany

Location

Staedtisches Klinikum Leipzig - Klinikum St. Georg gGmbH

Leipzig, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, Germany

Location

Gemeinschaftspraxis Dr. Goldmann/ Dr. Ebert

Lüneburg, Germany

Location

UniversitaetsMedizin Mannheim

Mannheim, Germany

Location

Klinikum Schwaebisch-Gmuend

Mutlangen, Germany

Location

Gemeinschaftspraxis Prof. Salat / Dr. Stötzer

München, Germany

Location

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

München, Germany

Location

Muencher Onkol. Praxis Elisenhof

München, Germany

Location

Onkologische Praxis Oldenburg

Oldenburg, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, Germany

Location

RoMed Klinikum Rosenheim

Rosenheim, Germany

Location

HELIOS Kliniken - HELIOS Klinik Rottweil

Rottweil, Germany

Location

HELIOS Kliniken - HELIOS Brustzentrums Nordachsen - HELIOS Klinik Schkeuditz

Schkeuditz, Germany

Location

Diakonie-Klinikum Schwäbisch Hall gGmbH

Schwäbisch Hall, Germany

Location

Leopoldina-Krankenhaus der Stadt Schweinfurt gGmbH

Schweinfurt, Germany

Location

Kliniken Landkreis Sigmaringen GmbH

Sigmaringen, Germany

Location

Klinikum Stuttgart

Stuttgart, Germany

Location

Klinikum Traunstein

Traunstein, Germany

Location

Gesellschaft für onkologische Studien, Praxismanagement und -Logistik

Troisdorf, Germany

Location

Eberhard Karls Universitaet Tuebingen - Universitaetsfrauenklinik Tuebingen

Tübingen, Germany

Location

Universitaetsklinikum Ulm

Ulm, Germany

Location

Gesundheitszentren Rhein-Neckar - GRN-Klinik Weinheim

Weinheim, Germany

Location

Onkologische Schwerpunktpraxis Wupperta

Wuppertal, Germany

Location

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27289552 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms; Neoplastic Cells, Circulating

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michail Ignatiadis, MD

  Institut Jules Bordet, Brussels, Belgium

  PRINCIPAL INVESTIGATOR

• Martine Piccart, MD

  Institut Jules Bordet, Brussels, Belgium

  STUDY CHAIR

• Christos Sotiriou, MD

  Institut Jules Bordet, Brussels, Belgium

  STUDY CHAIR

• Jean-Yves Pierga, MD

  Institut Curie, Paris, France

  STUDY CHAIR

• Brigitte Rack, MD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2012
• First Posted: March 8, 2012
• Study Start: April 1, 2013
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: March 13, 2019

Record last verified: 2019-03

Locations

FR (20); DE (50); BE (9); GB (1)