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

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2016 by University College, London
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01792726
First received: February 12, 2013
Last updated: August 15, 2016
Last verified: August 2016
  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.


Condition Intervention
Early Breast Cancer Radiation: Boost to the tumour bed

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).

  • 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.

  • Overall survival [ Time Frame: Five year median follow-up. ]
    Overall survival will be the time interval between randomisation and death.

  • 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.

  • Quality of life [ 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.


Estimated Enrollment: 1796
Study Start Date: June 2013
Estimated Study Completion Date: April 2022
Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Radiotherapy boost

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.
  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01792726

Contacts
Contact: Norman R Williams, PhD +44 (0)20 7679 9280 SITU.TARGITB@ucl.ac.uk
Contact: Haroon Miah +44 (0)20 7679 9280 SITU.TARGITB@ucl.ac.uk

Locations
United States, New York
Ashikari Breast Center Recruiting
Dobb's Ferry, New York, United States, 10522
Contact: Pond Kelemen, MD         
France
Institut Bergonié Recruiting
Bordeaux, France
Principal Investigator: Christel Breton-Callu, MD         
Centre Georges François Leclerc Recruiting
Dijon, France
Principal Investigator: Etienne Martin, MD         
Centre Léon Bérard Recruiting
Lyon, France
Principal Investigator: Christelle Faure, MD         
Hôpital Nord Recruiting
Marseille, France
Contact: Didier Cowen, MD         
Principal Investigator: Didier Cowen, MD         
Institut de Cancerologie de l'Ouest site René Gauducheau Recruiting
Nantes, France, 44805
Contact: Magali Le Blanc, MD         
Institut Universitaire du Cancer de Toulouse - Oncopole Recruiting
Toulouse, France
Contact: Francoise Izar, MD         
Principal Investigator: Francoise Izar, MD         
Italy
Centro Di Riferimento Oncologico Di Aviano Recruiting
Aviano, Italy
Contact: Samuele Massarut, MD         
Principal Investigator: Samuele Massarut, MD         
Istituto Oncologico Veneto Recruiting
Padova, Italy
Contact: Fabiana Gregucci         
Principal Investigator: Fernando Bozza         
Saudi Arabia
University of Dammam Recruiting
Dammam, Saudi Arabia
Principal Investigator: Maha Abdel Hadi         
Spain
Hospital Universitario Dr Negrín Recruiting
Las Palmas de Gran Canaria, Spain
Principal Investigator: Pedro C Lara, MD         
Switzerland
Brust-Zentrum Onkologie Recruiting
Zürich, Switzerland
Contact: Bärbel Papassotiropoulos         
United Kingdom
Princess Alexandra Hospital NHS Trust Recruiting
Harlow, United Kingdom
Principal Investigator: Julian Singer, MD         
Whittington Hospital Recruiting
London, United Kingdom, N19 5NF
Contact: Jayant S Vaidya, MBBS FRCS       jayant.vaidya@ucl.ac.uk   
Principal Investigator: Jayant S Vaidya, MBBS FRCS         
Royal Free London NHS Trust Recruiting
London, United Kingdom, NW3 2QG
Contact: Mo Keshtgar, MB BS       m.keshtgar@ucl.ac.uk   
Principal Investigator: Mo Keshtgar, MB BS         
Guy's Hospital Recruiting
London, United Kingdom
Contact: Sweta Sethi         
Principal Investigator: Michael Douek         
Hospital of St John and St Elizabeth Recruiting
London, United Kingdom
Contact: Mo Keshtgar, MB BS       m.keshtgar@ucl.ac.uk   
Principal Investigator: Mo Keshtgar, MB BS         
Princess Grace Hospital Recruiting
London, United Kingdom
Contact: Jayant S Vaidya, MB BS       jayant.vaidya@ucl.ac.uk   
Principal Investigator: Jayant S Vaidya, MB BS         
The Great Western Hospital Recruiting
Swindon, United Kingdom, SN3 6BB
Principal Investigator: Nathan Coombs, MB BS         
Sponsors and Collaborators
University College, London
National Institute for Health Research, United Kingdom
Investigators
Principal Investigator: Jayant S Vaidya, MBBS FRCS University College, London
  More Information

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01792726     History of Changes
Other Study ID Numbers: TARGIT Boost
NHS NIHR HTA ( Other Grant/Funding Number: 10/104/07 )
Study First Received: February 12, 2013
Last Updated: August 15, 2016

Keywords provided by University College, London:
breast cancer
radiotherapy
TARGIT
Intrabeam

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on June 26, 2017