Clinical Trials /

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

NCT01548677

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: EORTC-90091-10093
  • SECONDARY ID: 2009-017485-23
  • NCT ID: NCT01548677

Conditions

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

Interventions

DrugSynonymsArms
trastuzumabendocrine therapy, anti HER2 therapyHerceptin (trastuzumab)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
observationNo Intervention18 weeks
    Herceptin (trastuzumab)Experimental18 weeks
    • trastuzumab

    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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:CTC detection
    Time Frame:18 weeks post randomisation
    Safety Issue:
    Description:To compare circulating tumour cell (CTC)detection rate at week 18 between trastuzumab treatment arm and observational arm.

    Secondary Outcome Measures

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

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Completed
    Lead Sponsor:European Organisation for Research and Treatment of Cancer - EORTC

    Trial Keywords

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

    Last Updated

    January 24, 2018