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

July 10, 2019 updated by: University College, London

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.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

1796

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
          • Xinguang Wang
        • Principal Investigator:
          • Tao Ouyang
  • France
      • Bordeaux, France
        • Recruiting
        • Institut Bergonie
      • Caen, France
        • Recruiting
        • Centre Francois Baclesse
        • Contact:
        • Principal Investigator:
          • Serge Danhier, MD
      • Dijon, France
        • Recruiting
        • Centre Georges Francois Leclerc
        • Principal Investigator:
          • Etienne MARTIN, MD
      • Lyon, France
        • Recruiting
        • Centre Léon Bérard
        • Principal Investigator:
          • Christelle FAURE, MD
      • Marseille, France
        • Recruiting
        • Hôpital Nord
        • Contact:
          • Didier Cowen, MD
        • Principal Investigator:
          • Didier Cowen, MD
      • Nantes, France, 44805
        • Recruiting
        • Institut de Cancérologie de l'Ouest Site René Gauducheau
        • Contact:
          • Magali Le Blanc, MD
      • Toulouse, France
        • Recruiting
        • Institut Universitaire du Cancer de Toulouse - Oncopole
        • Contact:
          • Francoise Izar, MD
        • Principal Investigator:
          • Francoise Izar, MD
  • Italy
      • Aviano, Italy
        • Recruiting
        • Centro di Riferimento Oncologico di Aviano
        • Contact:
          • Samuele Massarut, MD
        • Principal Investigator:
          • Samuele Massarut, MD
      • Padova, Italy
        • Recruiting
        • Istituto Oncologico Veneto
        • Contact:
          • Fabiana Gregucci
        • Principal Investigator:
          • Fernando Bozza
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Recruiting
        • Gangnam Severance Hospital
        • Contact:
          • Sung Gwe Ahn
  • Malaysia
      • Kuala Lumpur, Malaysia
        • Recruiting
        • University Malaya Medical Centre
        • Contact:
        • Principal Investigator:
          • Nur Aishah Mohd Taib
  • Saudi Arabia
      • Dammam, Saudi Arabia
        • Recruiting
        • University of Dammam
        • Principal Investigator:
          • Maha Abdel Hadi
  • South Africa
      • Johannesburg, South Africa
        • Recruiting
        • Netcare Milpark Hospital
        • Contact:
          • Kyara Bergstrom
        • Principal Investigator:
          • Carol Benn
        • Sub-Investigator:
          • Yastira Ramdas
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Institut Catala d'Oncologia
        • Contact:
        • Principal Investigator:
          • Evelyn Martínez Pérez
      • Las Palmas de Gran Canaria, Spain
        • Recruiting
        • Hospital Universitario Dr Negrin
        • Principal Investigator:
          • Pedro C Lara, MD
  • Switzerland
      • Zürich, Switzerland
        • Recruiting
        • Brust-Zentrum Onkologie
        • Contact:
          • Bärbel Papassotiropoulos
  • Thailand
      • Bangkok, Thailand
        • Recruiting
        • Queen Sirikit Cantre for Breast Cancer
        • Contact:
          • Sikrit Denariyakoon
        • Principal Investigator:
          • Adhisabandh Chulakadabba
  • United Kingdom
      • Harlow, United Kingdom
        • Recruiting
        • Princess Alexandra Hospital NHS Trust
        • Principal Investigator:
          • Julian Singer, MD
      • London, United Kingdom, N19 5NF
        • Recruiting
        • Whittington Hospital
        • Contact:
        • Principal Investigator:
          • Jayant S Vaidya, MBBS FRCS
      • London, United Kingdom
        • Recruiting
        • Guy's Hospital
        • Contact:
          • Sweta Sethi
        • Principal Investigator:
          • Michael Douek
      • London, United Kingdom, NW3 2QG
        • Recruiting
        • Royal Free London NHS Trust
        • Contact:
        • Principal Investigator:
          • Mo Keshtgar, MB BS
      • London, United Kingdom
        • Recruiting
        • Hospital of St John and St Elizabeth
        • Contact:
        • Principal Investigator:
          • Mo Keshtgar, MB BS
      • London, United Kingdom
        • Active, not recruiting
        • Princess Grace Hospital
      • Swindon, United Kingdom, SN3 6BB
        • Recruiting
        • The Great Western Hospital
        • Principal Investigator:
          • Nathan Coombs, MB BS
      • Winchester, United Kingdom
        • Recruiting
        • Hampshire Hospitals NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Sanjay Raj
  • United States
    • California
      • Los Angeles, California, United States
        • Recruiting
        • Helen Rey Breast Cancer Research Foundation
        • Contact:
        • Principal Investigator:
          • Dennis R Holmes, MD
    • Georgia
      • Savannah, Georgia, United States
        • Active, not recruiting
        • Memorial Health University Medical Center
    • Michigan
      • Detroit, Michigan, United States
        • Recruiting
        • Beaumont Health - Royal Oak
        • Contact:
        • Principal Investigator:
          • Nayana Dekhne, MD
      • Saint Joseph, Michigan, United States
        • Recruiting
        • Lakeland Regional Health System
        • Contact:
        • Principal Investigator:
          • Benjamin T Gielda
    • New York
      • Dobbs Ferry, New York, United States, 10522
        • Recruiting
        • Ashikari Breast Center
        • Contact:
          • Pond Kelemen, MD
    • Ohio
      • Cleveland, Ohio, United States
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Principal Investigator:
          • Stephanie Valente
    • West Virginia
      • Morgantown, West Virginia, United States
        • Recruiting
        • West Virginia University
        • Contact:
        • Principal Investigator:
          • Geraldine Jacobson
    • Wisconsin
      • Green Bay, Wisconsin, United States
        • Recruiting
        • Aurora Breast Center
        • Contact:
        • Principal Investigator:
          • William Owens

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TARGIT
The 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.
Radiation: Boost to the tumour bed
Boost to the tumour bed, with whole breast EBRT delivered according to local policy.
Other Names:
  • Radiotherapy boost
Active Comparator: External beam radiotherapy boost
The 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.
Radiation: Boost to the tumour bed
Boost to the tumour bed, with whole breast EBRT delivered according to local policy.
Other Names:
  • Radiotherapy boost

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local tumour control (defined as no recurrent tumour in the ipsilateral breast).
Time Frame: Five year median follow-up
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.
Five year median follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Site of relapse within the treated breast
Time Frame: 5 years median follow-up
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).
5 years median follow-up
Relapse-free survival
Time Frame: Five year median follow-up
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.
Five year median follow-up
Overall survival
Time Frame: Five year median follow-up.
Overall survival will be the time interval between randomisation and death.
Five year median follow-up.
Adverse events related to the primary treatment of the breast cancer.
Time Frame: Five year median follow-up.
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.
Five year median follow-up.
Quality of life assessed by patient completed validated questionnaires.
Time Frame: Five year median follow-up
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.
Five year median follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

National Institute for Health Research, United Kingdom

Investigators

  • Principal Investigator: Jayant S Vaidya, MBBS FRCS, University College, London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (Anticipated)

January 1, 2022

Study Completion (Anticipated)

April 1, 2022

Study Registration Dates

First Submitted

February 12, 2013

First Submitted That Met QC Criteria

February 14, 2013

First Posted (Estimate)

February 15, 2013

Study Record Updates

Last Update Posted (Actual)

July 12, 2019

Last Update Submitted That Met QC Criteria

July 10, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TARGIT Boost
  • NHS NIHR HTA (Other Grant/Funding Number: 10/104/07)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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