Clinical trial NCT01548677: Efficacy Study of Herceptin to Treat HER2-negative CTC Breast Cancer
Official title: TRastuzumab in HER2-negative Early Breast Cancer as Adjuvant Treatment for Circulating Tumor Cells (CTC) ("TREAT CTC" Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Hoffmann-La Roche
name: Janssen Diagnostics, LLC
name: SUCCESS
name: UNICANCER
First posted: 2012-03-08
Enrollment: 1317
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: CTC detection
timeFrame: 18 weeks post randomisation
Secondary outcomes:
measure: RFI (recurrence free interval)
timeFrame: 2 years after LPI (last patient in)
measure: IDFS (Invasive Disease Free Survival)
timeFrame: 2 years after LPI
measure: DFS (disease free survival)
timeFrame: 2 years after LPI
measure: OS (overall survival)
timeFrame: 2 years after LPI
measure: CTC essay
timeFrame: 2 years after LPI
measure: CTC correlation
timeFrame: 2 years after LPI
measure: safety (cardiac)
timeFrame: 2 years after LPI
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis
city: Brussels
country: Belgium
facility: Hopital Universitaire Brugmann
city: Brussels
country: Belgium
facility: Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme
city: Brussels
country: Belgium
facility: Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet
city: Haine St Paul
country: Belgium
facility: Hopital De Jolimont
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Liege
country: Belgium
facility: C.H.U. Sart-Tilman
city: Namur
country: Belgium
facility: Clinique et Maternité Sainte Elisabeth
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Bordeaux
country: France
facility: Institut Bergonie
city: Brest
country: France
facility: CHU de Brest
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Contamine sur Arve
country: France
facility: Centre Hospitalier Alpes Léman
city: Draguignan
country: France
facility: Centre Hospitalier de la Dracénie
city: Grenoble
country: France
facility: CHU de Grenoble - La Tronche - Hôpital A. Michallon
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental Vendée
city: Le Chesnay
country: France
facility: Centre Hospitalier de Versailles - Hopital Andre Mignot
city: Limoges
country: France
facility: CHU de Limoges - Hopital Dupuytren
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Metz-Tessy
country: France
facility: Centre Hospitalier D'Annecy
city: Mont-de-Marsan
country: France
facility: Centre Hospitalier de Mont-de-Marsan
city: Nantes
country: France
facility: Centre Catherine De Sienne
city: Paris
country: France
facility: Institut Curie
city: Saint-Cloud
country: France
facility: Institut Curie - Hopital Rene Huguenin
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg - Hôpitaux Universitaires de Strasbourg - Hôpital civil
city: Thonon les Bains
country: France
facility: Hopitaux du Leman - Site Georges Pianta
city: Valence
country: France
facility: CH de Valence
city: Vandoeuvre-Les-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Gustave Roussy
city: Amberg
country: Germany
facility: Klinikum St. Marien
city: Augsburg
country: Germany
facility: Gemeinschaftspraxis Augsburg
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Berlin
country: Germany
facility: Praxisklinik Krebsheilkunde für Frauen
city: Boeblingen
country: Germany
facility: Klinikum Sindelfingen-Boeblingen
city: Bonn
country: Germany
facility: Medizinischen Zentrum Bonn
city: Bottrop
country: Germany
facility: Marienhospital Bottrop gGmbH
city: Braunschweig
country: Germany
facility: Gemeinschaftspraxis Lorenz / Hecker / Wesche
city: Bremen
country: Germany
facility: Onkologische-Hämatologischen Schwerpunktpraxis
city: Dresden
country: Germany
facility: Onkologische Gemeinschaftspraxis
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Luisenkrankenhaus GmbH & Co. KG
city: Duesseldorf
country: Germany
facility: Universitaetsklinik Duesseldorf
city: Erlangen
country: Germany
facility: Universitaetsklinik Erlangen
city: Essen
country: Germany
facility: Universitaetsklinikum - Essen
city: Esslingen
country: Germany
facility: Staedtische Kliniken
city: Flensburg
country: Germany
facility: Ev.-Luth. Diakonissenanstalt Flensburg
city: Frankfurt Am Main
country: Germany
facility: Staedtische Kliniken Frankfurt Am Main-Hoechst
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Hamburg
country: Germany
facility: Universitaets-Krankenhaus Eppendorf
city: Hannover
country: Germany
facility: Gynäkologisch-Onkologischen Schwerpunktpraxis
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hildesheim
country: Germany
facility: Gemeinschaftspraxis Dr. Pourfard / Dr. Uleer
city: Karlsruhe
country: Germany
facility: St. Marien-Klinik GmbH Frauenklinik der St. Vincentius-Kliniken gAG
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Kiel
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Landshut
country: Germany
facility: Klinikum Landshut
city: Leipzig
country: Germany
facility: Staedtisches Klinikum Leipzig - Klinikum St. Georg gGmbH
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
city: Lueneburg
country: Germany
facility: Gemeinschaftspraxis Dr. Goldmann/ Dr. Ebert
city: Mannheim
country: Germany
facility: UniversitaetsMedizin Mannheim
city: Muenchen
country: Germany
facility: Gemeinschaftspraxis Prof. Salat / Dr. Stötzer
city: Muenchen
country: Germany
facility: Ludwig-Maximilians-Universitaet Muenchen - Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe - Innenstadt
city: Muenchen
country: Germany
facility: Muencher Onkol. Praxis Elisenhof
city: Mutlangen
country: Germany
facility: Klinikum Schwaebisch-Gmuend
city: Oldenburg
country: Germany
facility: Onkologische Praxis Oldenburg
city: Ravensburg
country: Germany
facility: Studienzentrum Onkologie Ravensburg
city: Rosenheim
country: Germany
facility: RoMed Klinikum Rosenheim
city: Rottweil
country: Germany
facility: HELIOS Kliniken - HELIOS Klinik Rottweil
city: Schkeuditz
country: Germany
facility: HELIOS Kliniken - HELIOS Brustzentrums Nordachsen - HELIOS Klinik Schkeuditz
city: Schwaebisch Hall
country: Germany
facility: Diakonie-Klinikum Schwäbisch Hall gGmbH
city: Schweinfurt
country: Germany
facility: Leopoldina-Krankenhaus der Stadt Schweinfurt gGmbH
city: Sigmaringen
country: Germany
facility: Kliniken Landkreis Sigmaringen GmbH
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
city: Traunstein
country: Germany
facility: Klinikum Traunstein
city: Troisdorf
country: Germany
facility: Gesellschaft für onkologische Studien, Praxismanagement und -Logistik
city: Tuebingen
country: Germany
facility: Eberhard Karls Universitaet Tuebingen - Universitaetsfrauenklinik Tuebingen
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Weinheim
country: Germany
facility: Gesundheitszentren Rhein-Neckar - GRN-Klinik Weinheim
city: Wuppertal
country: Germany
facility: Onkologische Schwerpunktpraxis Wupperta
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust - Churchill Hospital
Study officials:
affiliation: Institut Jules Bordet, Brussels, Belgium
name: Michail Ignatiadis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Jules Bordet, Brussels, Belgium
name: Martine Piccart, MD
role: STUDY_CHAIR
affiliation: Institut Jules Bordet, Brussels, Belgium
name: Christos Sotiriou, MD
role: STUDY_CHAIR
affiliation: Institut Curie, Paris, France
name: Jean-Yves Pierga, MD
role: STUDY_CHAIR
affiliation: Ludwig-Maximilians-Universitaet Muenchen - Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe - Innenstadt, Munich, Germany
name: Brigitte Rack, MD
role: STUDY_CHAIR
References:
citation: 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.