Clinical trial NCT01792726: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Early Breast Cancer
Keywords: breast cancer
radiotherapy
TARGIT
Intrabeam
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2013-02-15
Enrollment: 1796
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Local tumour control (defined as no recurrent tumour in the ipsilateral breast).
timeFrame: Five year median follow-up
Secondary outcomes:
measure: Site of relapse within the treated breast
timeFrame: 5 years median follow-up
measure: Relapse-free survival
timeFrame: Five year median follow-up
measure: Overall survival
timeFrame: Five year median follow-up.
measure: Adverse events related to the primary treatment of the breast cancer.
timeFrame: Five year median follow-up.
measure: Quality of life assessed by patient completed validated questionnaires.
timeFrame: Five year median follow-up
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Helen Rey Breast Cancer Research Foundation
state: California
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Detroit
country: United States
facility: Beaumont Health - Royal Oak
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Regional Health System
state: Michigan
city: Dobbs Ferry
country: United States
facility: Ashikari Breast Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Green Bay
country: United States
facility: Aurora Breast Center
state: Wisconsin
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital Nord
city: Nantes
country: France
facility: Institut de Cancerologie de l'Ouest site René Gauducheau
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - Oncopole
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico Di Aviano
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Dammam
country: Saudi Arabia
facility: University of Dammam
city: Johannesburg
country: South Africa
facility: Netcare Milpark Hospital
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Dr Negrín
city: Zürich
country: Switzerland
facility: Brust-Zentrum Onkologie
city: Bangkok
country: Thailand
facility: Queen Sirikit Cantre for Breast Cancer
city: Harlow
country: United Kingdom
facility: Princess Alexandra Hospital NHS Trust
city: London
country: United Kingdom
facility: Whittington Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Trust
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Hospital of St John and St Elizabeth
city: London
country: United Kingdom
facility: Princess Grace Hospital
city: Swindon
country: United Kingdom
facility: The Great Western Hospital
city: Winchester
country: United Kingdom
facility: Hampshire Hospitals NHS Foundation Trust
Study officials:
affiliation: University College, London
name: Jayant S Vaidya, MBBS FRCS
role: PRINCIPAL_INVESTIGATOR
References: