Clinical Trials /

A Comparison of Intra-operative Radiotherapy Boost With External Beam Radiotherapy Boost in Early Breast Cancer.

NCT01792726

Description:

TARGIT-Boost is an international randomised clinical trial designed to test the hypothesis that the tumour bed boost delivered as a single dose of targeted intraoperative radiotherapy (TARGIT-B) is superior to the conventional course of external beam radiotherapy boost (EBRT-Boost), especially in women with high risk of local recurrence. It is a pragmatic trial in which each participating centre can use the local predefined inclusion/exclusion criteria for entry into the trial. Only centres with access to the Intrabeam® (Carl Zeiss) are eligible to enter patients into the trial. Eligible patients are those with a higher risk of local recurrence after breast conserving surgery. After giving consent patients are randomised to either TARGIT Boost or EBRT Boost. All patients will receive whole breast EBRT. They may receive any other adjuvant treatments as deemed necessary. The protocol recommends that patients be followed at six monthly intervals for three years and then annually. The primary endpoint is ipsilateral breast recurrence rate. Secondary endpoints are relapse-free survival, site of recurrence, overall survival (breast-cancer specific and non-breast cancer deaths) patient satisfaction and quality of life.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

URL:

https://clinicaltrials.gov/show/NCT01792726

Trial Eligibility

Document

Title

  • Brief Title: A Comparison of Intra-operative Radiotherapy Boost With External Beam Radiotherapy Boost in Early Breast Cancer.
  • Official Title: An International Randomised Controlled Trial to Compare Targeted Intra-operative Radiotherapy Boost With Conventional External Beam Radiotherapy Boost After Lumpectomy for Breast Cancer in Women With a High Risk of Local Recurrence.

Clinical Trial IDs

  • ORG STUDY ID: TARGIT Boost
  • SECONDARY ID: NHS NIHR HTA
  • NCT ID: NCT01792726

Conditions

  • Early Breast Cancer

Purpose

TARGIT-Boost is an international randomised clinical trial designed to test the hypothesis that the tumour bed boost delivered as a single dose of targeted intraoperative radiotherapy (TARGIT-B) is superior to the conventional course of external beam radiotherapy boost (EBRT-Boost), especially in women with high risk of local recurrence. It is a pragmatic trial in which each participating centre can use the local predefined inclusion/exclusion criteria for entry into the trial. Only centres with access to the Intrabeam® (Carl Zeiss) are eligible to enter patients into the trial. Eligible patients are those with a higher risk of local recurrence after breast conserving surgery. After giving consent patients are randomised to either TARGIT Boost or EBRT Boost. All patients will receive whole breast EBRT. They may receive any other adjuvant treatments as deemed necessary. The protocol recommends that patients be followed at six monthly intervals for three years and then annually. The primary endpoint is ipsilateral breast recurrence rate. Secondary endpoints are relapse-free survival, site of recurrence, overall survival (breast-cancer specific and non-breast cancer deaths) patient satisfaction and quality of life.

Detailed Description

      DESIGN: A pragmatic multi-centre randomised clinical trial to test whether TARGeted
      Intraoperative radioTherapy as a tumour bed Boost (TARGIT-B) is superior in terms of local
      relapse within the treated breast compared with standard post-operative external beam
      radiotherapy boost in women undergoing breast conserving therapy who have a higher risk of
      local recurrence. Patients can be entered before the primary surgery or in a smaller
      proportion of cases, post-pathology. SETTING: Specialist breast units in UK, USA, Canada,
      Australia and Europe; 31 centres currently recruiting in the TARGIT-A trial and several are
      ready to join. TARGET POPULATION: Breast cancer patients suitable for breast conserving
      surgery, but with a high risk of local recurrence. Details of inclusion and exclusion are
      given in part 2. Briefly the patients should be either younger than 45 or if older, need to
      have certain pathological features that confer a high risk of local recurrence of breast
      cancer. HEALTH TECHNOLOGIES BEING ASSESSED. The TARGIT Technique: The Intrabeam® (Carl Zeiss,
      FDA approved and CE marked) is a miniature electron beam-driven source which provides a point
      source of low energy X-rays (50kV maximum) at the tip of a 3.2mm diameter tube. The radiation
      source is inserted into the tumour bed immediately after excision of the tumour and switched
      on for 20-35 minutes to provide intra-operative radiotherapy accurately targeted to the
      tissues that are at highest risk of local recurrence. The physics, dosimetry and early
      clinical applications of this soft x-ray device have been well studied. For use in the
      breast, the technique was first developed and piloted at University College London. The
      radiation source is surrounded by a spherical applicator, specially designed (and available
      in various sizes) to produce a uniform field of radiation at its surface, enabling delivery
      of an accurately calculated dose to a prescribed depth. It is inserted in the tumour bed and
      apposed to it with surgical sutures and/or other means. As the x-rays rapidly attenuate the
      dose to more distant tissues is reduced; this also allows it to be used in standard operating
      theatres. 20 Gy is delivered to the tumour bed surface in 20-35 minutes, after which the
      radiation is switched off, the applicator removed, and the wound closed in the normal way.
      This simple technique has potentially several advantages over convential external beam
      radiotherapy, interstitial implantation of radioactive wires or conformal external beam
      radiotherapy. The first pilot of twenty-five cases was at performed at UCL using TARGIT
      technique as a replacement for the boost dose of radiotherapy; full dose external beam
      treatment was subsequently given. The phase II study of 300 patients was published and
      recently updated with long term data along with favourable toxicity and cosmetic outcome
      results of individual cohorts. A mathematical model of TARGIT developed recently (funded by
      Cancer Research UK) suggests that it could be superior to conventional radiotherapy.
      Translational research has found that TARGIT impairs the surgical-trauma-stimulated
      proliferation and invasiveness of breast cancer cells. This effect of radiotherapy may act
      synergistically with its tumouricidal effect yielding a superior result. MEASUREMENT OF COST
      AND OUTCOME: Patient assessments will be clinical examination (6 monthly x 3 years then
      yearly x 10 years) and mammography (yearly). with ulstrasound (if needed) . Primary outcome:
      histologically/cytologically proven local recurrence. Secondary: site of relapse in the
      breast, overall survival, local toxicity (RTOG and LENT SOMA criteria), cosmesis, quality of
      life, patient satisfaction and health economics. The cost and cost-effectiveness of TARGIT
      versus EBRT, both as boost, will be calculated from a NHS and personal social services (PSS)
      perspective. Costs directly incurred by patients will also be assesed, since EBRT as a boost
      is likely to impose additional time and travel expense to patients and families.

Trial Arms

NameTypeDescriptionInterventions
TARGITExperimentalThe experimental policy is to give targeted intra-operative radiotherapy (TARGIT-Boost) in a single dose to substitute for the usual boost dose, in addition to whole breast external beam radiotherapy delivered according to local treatment guidelines.
    External beam radiotherapy boostActive ComparatorThe conventional policy is to receive radiation boost to the tumour bed delivered by external beam radiotherapy (EBRT) in addition to whole breast external beam radiotherapy delivered according to local treatment guidelines.

      Eligibility Criteria

              Inclusion Criteria:

        At least one of these criteria must be satisfied:

          1. Less than 46 years of age

          2. More than 45 years of age, but with one of the following poor prognostic factors:

               1. lymphovascular invasion

               2. gross nodal involvement (not micrometastasis)

               3. more than one tumour in the breast but still suitable for breast conserving
                  surgery through a single specimen

          3. More than 45 years of age, but with at least two of the following poor prognostic
             factors

               1. ER and/or PgR negative

               2. Grade 3 histology

               3. Positive margins at first excision

          4. Those patients with large tumours which have responded to neo-adjuvant chemo- or
             hormone therapy in an attempt to shrink the tumour and are suitable for breast
             conserving surgery as a result.

          5. Lobular carcinoma or Extensive Intraductal Component (EIC)

          6. A list (one to many) of high risk factors are present (as predefined in the policy
             document) that give a high risk of local recurrence.

          7. Patients with either HER2 positive or HER2 negative can be included.

        Exclusion Criteria:

          1. Bilateral breast cancer at the time of diagnosis.

          2. Patients with any severe concomitant disease that may limit their life expectancy

          3. Previous history of malignant disease does not preclude entry if the expectation of
             relapse-free survival at 10 years is 90% or greater (e.g., non-melanoma skin cancer,
             CIN, etc).

          4. No more than 30 days can have elapsed between last breast cancer surgery (not
             axillary) and randomisation for patients in the post-pathology stratification unless
             part of a specific clinical trial that addresses the question of timing or tumour bed
             can be reliably identified, e.g., by ultrasound.
      Maximum Eligible Age:N/A
      Minimum Eligible Age:N/A
      Eligible Gender:Female
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Local tumour control (defined as no recurrent tumour in the ipsilateral breast).
      Time Frame:Five year median follow-up
      Safety Issue:
      Description:To evaluate whether a tumour bed boost in the form of a single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence is superior (in terms of local tumour control) to standard post-operative external beam radiotherapy boost, after breast conserving surgery in women undergoing breast conserving therapy who have a higher risk of local recurrence.

      Secondary Outcome Measures

      Measure:Site of relapse within the treated breast
      Time Frame:5 years median follow-up
      Safety Issue:
      Description:Site of relapse within the breast will be recorded in order to assess whether the recurrence is at the site of the initial tumour or at a new site and whether it has occurred within the treated field (TARGIT or EBRT boost).
      Measure:Relapse-free survival
      Time Frame:Five year median follow-up
      Safety Issue:
      Description:Relapse-free survival will be recorded as the time interval between randomisation and the date of confirmation of recurrence. The actual date to be used is the clinic day on which the investigations that led to a confirmed diagnosis of the recurrence were requested. Relapse-free survival will include any recurrence of breast cancer or death without a prior report of relapse.
      Measure:Overall survival
      Time Frame:Five year median follow-up.
      Safety Issue:
      Description:Overall survival will be the time interval between randomisation and death.
      Measure:Adverse events related to the primary treatment of the breast cancer.
      Time Frame:Five year median follow-up.
      Safety Issue:
      Description:Local toxicity and morbidity will be recorded as adverse events related to the primary treatment of the breast cancer. Quality of life will be assessed though validated patient-completed questionnaires.
      Measure:Quality of life assessed by patient completed validated questionnaires.
      Time Frame:Five year median follow-up
      Safety Issue:
      Description:The primary patient reported outcome endpoint for quality of life will be the FACT-B+4 trial outcome index (TOI) score. The TOI score (0-180) is a sum of the scores of the 27 items included in the physical well-being, functional well-being and breast cancer subscales of the FACT-B+4. A change of at least 5 points in TOI is considered to be clinically relevant or a minimally important difference (Eton et al. 2004). Secondary endpoints will be: 1) the five item arm functioning subscale score (0-20) 2) The 40 item FACT B+4 score (0-160), which reflects global quality of life including social and emotional well-being.

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:University College, London

      Trial Keywords

      • breast cancer
      • radiotherapy
      • TARGIT
      • Intrabeam

      Last Updated

      July 12, 2019