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

• ClinicalTrials.gov Identifier: NCT01548677
• Recruitment Status: Completed
• First Posted: March 8, 2012
• Last Update Posted: March 13, 2019
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Hoffmann-La Roche; Janssen Diagnostics, LLC; SUCCESS; UNICANCER
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information

• First Submitted Date: March 5, 2012
• First Posted Date: March 8, 2012
• Last Update Posted Date: March 13, 2019
• Study Start Date: April 2013
• Actual Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2012)

CTC detection [ Time Frame: 18 weeks post randomisation ]

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

Original Primary Outcome Measures (submitted: March 5, 2012)

CTC detection [ Time Frame: 18 weeks post randomisation ]

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

Current Secondary Outcome Measures (submitted: March 8, 2012)

• RFI (recurrence free interval) [ Time Frame: 2 years after LPI (last patient in) ]
  Recurrence Free Interval (RFI) (key secondary endpoint) between trastuzumab and observation
• IDFS (Invasive Disease Free Survival) [ Time Frame: 2 years after LPI ]
  Invasive Disease Free Survival between trastuzumab and observation
• DFS (disease free survival) [ Time Frame: 2 years after LPI ]
  Disease Free survival between trastuzumab and observation
• OS (overall survival) [ Time Frame: 2 years after LPI ]
  Overall Survival between trastuzumab and observation
• CTC essay [ Time Frame: 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)
• CTC correlation [ Time Frame: 2 years after LPI ]
  To correlate CTC detection rate at baseline and/or week 18 with RFI, IDFS, DFS, OS
• safety (cardiac) [ Time Frame: 2 years after LPI ]
  To assess safety, especially cardiac safety, of trastuzumab in women with HER2 negative primary tumors and CTC

Original Secondary Outcome Measures (submitted: March 5, 2012)

• RFI [ Time Frame: 2 years after LPI ]
  Recurrence Free Interval (RFI) (key secondary endpoint) between trastuzumab and observation
• IDFS [ Time Frame: 2 years after LPI ]
  Invasive Disease Free Survival between trastuzumab and observation
• DFS [ Time Frame: 2 years after LPI ]
  Disease Free survival between trastuzumab and observation
• OS [ Time Frame: 2 years after LPI ]
  Overall Survival between trastuzumab and observation
• CTC essay [ Time Frame: 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)
• CTC correlation [ Time Frame: 2 years after LPI ]
  To correlate CTC detection rate at baseline and/or week 18 with RFI, IDFS, DFS, OS
• safety (cardiac) [ Time Frame: 2 years after LPI ]
  To assess safety, especially cardiac safety, of trastuzumab in women with HER2 negative primary tumors and CTC

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

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.

Other Names:

• endocrine therapy
• anti HER2 therapy

Study Arms

• No Intervention: observation
  18 weeks
• Experimental: Herceptin (trastuzumab)
  18 weeks
  Intervention: Drug: trastuzumab

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 24, 2018): 1317
• Original Estimated Enrollment (submitted: March 5, 2012): 2175
• Actual Study Completion Date: March 2017
• Actual Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Germany, United Kingdom

Administrative Information

• NCT Number: NCT01548677
• Other Study ID Numbers: EORTC-90091-10093; 2009-017485-23 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• Original Responsible Party: Same as current
• Current Study Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: European Organisation for Research and Treatment of Cancer - EORTC
• Verification Date: March 2019