Clincosm LogoSign in Get a demo

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

Sponsor
European Organisation for Research and Treatment of Cancer - EORTC (Other)
Overall Status
Completed
CT.gov ID
NCT01548677
Collaborator
Hoffmann-La Roche (Industry), Janssen Diagnostics, LLC (Industry), SUCCESS (Other), UNICANCER (Other)
1,317
Enrollment
80
Locations
2
Arms
47
Duration (Months)
16.5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
1317 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
TRastuzumab in HER2-negative Early Breast Cancer as Adjuvant Treatment for Circulating Tumor Cells (CTC) ("TREAT CTC" Trial)
Study Start Date :
Apr 1, 2013
Actual Primary Completion Date :
Mar 1, 2017
Actual Study Completion Date :
Mar 1, 2017

Arms and Interventions

Arm Intervention/Treatment
No Intervention: observation

18 weeks
Experimental: Herceptin (trastuzumab)

18 weeks

Drug: 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.
Other Names:
  • endocrine therapy
  • anti HER2 therapy

    		•

    Outcome Measures

    Primary Outcome Measures

    1. CTC detection [18 weeks post randomisation]

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

    Secondary Outcome Measures

    1. RFI (recurrence free interval) [2 years after LPI (last patient in)]

      Recurrence Free Interval (RFI) (key secondary endpoint) between trastuzumab and observation

    2. IDFS (Invasive Disease Free Survival) [2 years after LPI]

      Invasive Disease Free Survival between trastuzumab and observation

    3. DFS (disease free survival) [2 years after LPI]

      Disease Free survival between trastuzumab and observation

    4. OS (overall survival) [2 years after LPI]

      Overall Survival between trastuzumab and observation

    5. CTC essay [2 years after LPI]

      To evaluate in a clinical trial setting the feasibility, reliability, within patient reproducibility and variability of the assay for CTC(s)

    6. CTC correlation [2 years after LPI]

      To correlate CTC detection rate at baseline and/or week 18 with RFI, IDFS, DFS, OS

    7. safety (cardiac) [2 years after LPI]

      To assess safety, especially cardiac safety, of trastuzumab in women with HER2 negative primary tumors and CTC

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Onze Lieve Vrouw Ziekenhuis Aalst Belgium
    2 Hopital Universitaire Brugmann Brussels Belgium
    3 Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme Brussels Belgium
    4 Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet Brussels Belgium
    5 Hopital De Jolimont Haine St Paul Belgium
    6 U.Z. Leuven - Campus Gasthuisberg Leuven Belgium
    7 C.H.U. Sart-Tilman Liege Belgium
    8 Clinique et Maternité Sainte Elisabeth Namur Belgium
    9 AZ Damiaan Oostende Belgium
    10 Institut Bergonie Bordeaux France
    11 CHU de Brest Brest France
    12 Centre Regional Francois Baclesse Caen France
    13 Centre Hospitalier Alpes Léman Contamine sur Arve France
    14 Centre Hospitalier de la Dracénie Draguignan France
    15 CHU de Grenoble - La Tronche - Hôpital A. Michallon Grenoble France
    16 Centre Hospitalier Departemental Vendée La Roche Sur Yon France
    17 Centre Hospitalier de Versailles - Hopital Andre Mignot Le Chesnay France
    18 CHU de Limoges - Hopital Dupuytren Limoges France
    19 Clinique de la Sauvegarde Lyon France
    20 Centre Hospitalier D'Annecy Metz-Tessy France
    21 Centre Hospitalier de Mont-de-Marsan Mont-de-Marsan France
    22 Centre Catherine De Sienne Nantes France
    23 Institut Curie Paris France
    24 Institut Curie - Hopital Rene Huguenin Saint-Cloud France
    25 Hopitaux Universitaires de Strasbourg - Hôpitaux Universitaires de Strasbourg - Hôpital civil Strasbourg France
    26 Hopitaux du Leman - Site Georges Pianta Thonon les Bains France
    27 CH de Valence Valence France
    28 Institut de Cancérologie de Lorraine Vandoeuvre-Les-Nancy France
    29 Gustave Roussy Villejuif France
    30 Klinikum St. Marien Amberg Germany
    31 Gemeinschaftspraxis Augsburg Augsburg Germany
    32 Klinikum Augsburg Augsburg Germany
    33 Praxisklinik Krebsheilkunde für Frauen Berlin Germany
    34 Klinikum Sindelfingen-Boeblingen Boeblingen Germany
    35 Medizinischen Zentrum Bonn Bonn Germany
    36 Marienhospital Bottrop gGmbH Bottrop Germany
    37 Gemeinschaftspraxis Lorenz / Hecker / Wesche Braunschweig Germany
    38 Onkologische-Hämatologischen Schwerpunktpraxis Bremen Germany
    39 Onkologische Gemeinschaftspraxis Dresden Germany
    40 Universitaetsklinikum Carl Gustav Carus Dresden Germany
    41 Luisenkrankenhaus GmbH & Co. KG Duesseldorf Germany
    42 Universitaetsklinik Duesseldorf Duesseldorf Germany
    43 Universitaetsklinik Erlangen Erlangen Germany
    44 Universitaetsklinikum - Essen Essen Germany
    45 Staedtische Kliniken Esslingen Germany
    46 Ev.-Luth. Diakonissenanstalt Flensburg Flensburg Germany
    47 Staedtische Kliniken Frankfurt Am Main-Hoechst Frankfurt Am Main Germany
    48 Universitaetsklinikum Freiburg Freiburg Germany
    49 Universitaets-Krankenhaus Eppendorf Hamburg Germany
    50 Gynäkologisch-Onkologischen Schwerpunktpraxis Hannover Germany
    51 Medizinische Hochschule Hannover Hannover Germany
    52 Gemeinschaftspraxis Dr. Pourfard / Dr. Uleer Hildesheim Germany
    53 St. Marien-Klinik GmbH Frauenklinik der St. Vincentius-Kliniken gAG Karlsruhe Germany
    54 Universitaetsklinikum Schleswig-Holstein - Campus Kiel Kiel Germany
    55 Universitaetsklinikum Koeln Koeln Germany
    56 Klinikum Landshut Landshut Germany
    57 Staedtisches Klinikum Leipzig - Klinikum St. Georg gGmbH Leipzig Germany
    58 Klinikum Ludwigsburg Ludwigsburg Germany
    59 Gemeinschaftspraxis Dr. Goldmann/ Dr. Ebert Lueneburg Germany
    60 UniversitaetsMedizin Mannheim Mannheim Germany
    61 Gemeinschaftspraxis Prof. Salat / Dr. Stötzer Muenchen Germany
    62 Ludwig-Maximilians-Universitaet Muenchen - Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe - Innenstadt Muenchen Germany
    63 Muencher Onkol. Praxis Elisenhof Muenchen Germany
    64 Klinikum Schwaebisch-Gmuend Mutlangen Germany
    65 Onkologische Praxis Oldenburg Oldenburg Germany
    66 Studienzentrum Onkologie Ravensburg Ravensburg Germany
    67 RoMed Klinikum Rosenheim Rosenheim Germany
    68 HELIOS Kliniken - HELIOS Klinik Rottweil Rottweil Germany
    69 HELIOS Kliniken - HELIOS Brustzentrums Nordachsen - HELIOS Klinik Schkeuditz Schkeuditz Germany
    70 Diakonie-Klinikum Schwäbisch Hall gGmbH Schwaebisch Hall Germany
    71 Leopoldina-Krankenhaus der Stadt Schweinfurt gGmbH Schweinfurt Germany
    72 Kliniken Landkreis Sigmaringen GmbH Sigmaringen Germany
    73 Klinikum Stuttgart Stuttgart Germany
    74 Klinikum Traunstein Traunstein Germany
    75 Gesellschaft für onkologische Studien, Praxismanagement und -Logistik Troisdorf Germany
    76 Eberhard Karls Universitaet Tuebingen - Universitaetsfrauenklinik Tuebingen Tuebingen Germany
    77 Universitaetsklinikum Ulm Ulm Germany
    78 Gesundheitszentren Rhein-Neckar - GRN-Klinik Weinheim Weinheim Germany
    79 Onkologische Schwerpunktpraxis Wupperta Wuppertal Germany
    80 Oxford University Hospitals NHS Trust - Churchill Hospital Oxford United Kingdom

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Michail Ignatiadis, MD, Institut Jules Bordet, Brussels, Belgium
    • Study Chair: 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 Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    European Organisation for Research and Treatment of Cancer - EORTC
    ClinicalTrials.gov Identifier:
    NCT01548677
    Other Study ID Numbers:
    • EORTC-90091-10093
    • 2009-017485-23
    First Posted:
    Mar 8, 2012
    Last Update Posted:
    Mar 13, 2019
    Last Verified:
    Mar 1, 2019
    Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC
    Circulating Tumour Cells
    HER2 negative primary breast cancer
    HER2 positive CTC
    Trastuzumab
    Additional relevant MeSH terms:
    Breast Neoplasms
    Neoplastic Cells, Circulating
    Trastuzumab

    Study Results

    No Results Posted as of Mar 13, 2019