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

Breast Cancer Clinical Trial

— TREAT-CTC  

Official title:

TRastuzumab in HER2-negative Early Breast Cancer as Adjuvant Treatment for Circulating Tumor Cells (CTC) ("TREAT CTC" Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01548677
• Other study ID #: EORTC-90091-10093
• Secondary ID: 2009-017485-23
• Status: Completed
• Phase: Phase 2
• Start date: April 2013
• Est. completion date: March 2017

Study information

• Verified date: March 2019
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1317
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

• 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Circulating Tumor Cells
• Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
• Neoplastic Cells, Circulating

Intervention

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.

Locations

Country	Name	City	State
Belgium	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 St Paul
Belgium	U.Z. Leuven - Campus Gasthuisberg	Leuven
Belgium	C.H.U. Sart-Tilman	Liege
Belgium	Clinique et Maternité Sainte Elisabeth	Namur
Belgium	AZ Damiaan	Oostende
France	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	Vandoeuvre-Les-Nancy
France	Gustave Roussy	Villejuif
Germany	Klinikum St. Marien	Amberg
Germany	Gemeinschaftspraxis Augsburg	Augsburg
Germany	Klinikum Augsburg	Augsburg
Germany	Praxisklinik Krebsheilkunde für Frauen	Berlin
Germany	Klinikum Sindelfingen-Boeblingen	Boeblingen
Germany	Medizinischen Zentrum Bonn	Bonn
Germany	Marienhospital Bottrop gGmbH	Bottrop
Germany	Gemeinschaftspraxis Lorenz / Hecker / Wesche	Braunschweig
Germany	Onkologische-Hämatologischen Schwerpunktpraxis	Bremen
Germany	Onkologische Gemeinschaftspraxis	Dresden
Germany	Universitaetsklinikum Carl Gustav Carus	Dresden
Germany	Luisenkrankenhaus GmbH & Co. KG	Duesseldorf
Germany	Universitaetsklinik Duesseldorf	Duesseldorf
Germany	Universitaetsklinik Erlangen	Erlangen
Germany	Universitaetsklinikum - Essen	Essen
Germany	Staedtische Kliniken	Esslingen
Germany	Ev.-Luth. Diakonissenanstalt Flensburg	Flensburg
Germany	Staedtische Kliniken Frankfurt Am Main-Hoechst	Frankfurt Am Main
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Universitaets-Krankenhaus Eppendorf	Hamburg
Germany	Gynäkologisch-Onkologischen Schwerpunktpraxis	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
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	Universitaetsklinikum Koeln	Koeln
Germany	Klinikum Landshut	Landshut
Germany	Staedtisches Klinikum Leipzig - Klinikum St. Georg gGmbH	Leipzig
Germany	Klinikum Ludwigsburg	Ludwigsburg
Germany	Gemeinschaftspraxis Dr. Goldmann/ Dr. Ebert	Lueneburg
Germany	UniversitaetsMedizin Mannheim	Mannheim
Germany	Gemeinschaftspraxis Prof. Salat / Dr. Stötzer	Muenchen
Germany	Ludwig-Maximilians-Universitaet Muenchen - Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe - Innenstadt	Muenchen
Germany	Muencher Onkol. Praxis Elisenhof	Muenchen
Germany	Klinikum Schwaebisch-Gmuend	Mutlangen
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	Schwaebisch 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	Tuebingen
Germany	Universitaetsklinikum Ulm	Ulm
Germany	Gesundheitszentren Rhein-Neckar - GRN-Klinik Weinheim	Weinheim
Germany	Onkologische Schwerpunktpraxis Wupperta	Wuppertal
United Kingdom	Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford

Sponsors (5)

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

Countries where clinical trial is conducted

Belgium,  France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	RFI (recurrence free interval)	Recurrence Free Interval (RFI) (key secondary endpoint) between trastuzumab and observation	2 years after LPI (last patient in)
Secondary	IDFS (Invasive Disease Free Survival)	Invasive Disease Free Survival between trastuzumab and observation	2 years after LPI
Secondary	DFS (disease free survival)	Disease Free survival between trastuzumab and observation	2 years after LPI
Secondary	OS (overall survival)	Overall Survival between trastuzumab and observation	2 years after LPI
Secondary	CTC essay	To evaluate in a clinical trial setting the feasibility, reliability, within patient reproducibility and variability of the assay for CTC(s)	2 years after LPI
Secondary	CTC correlation	To correlate CTC detection rate at baseline and/or week 18 with RFI, IDFS, DFS, OS	2 years after LPI
Secondary	safety (cardiac)	To assess safety, especially cardiac safety, of trastuzumab in women with HER2 negative primary tumors and CTC	2 years after LPI

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