Condition category
Cancer
Date applied
21/07/2004
Date assigned
21/09/2004
Last edited
03/10/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Norman Williams

ORCID ID

Contact details

Clinical Trials Group
UCL Medical School
Centre for Clinical Science and Technology
Clerkenwell Building
Whittington Campus
Highgate Hill
London
N19 5LW
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00983684

Protocol/serial number

HTA 07/60/49

Study information

Scientific title

TARGIT: a randomised controlled trial to compare targeted intra-operative radiotherapy with conventional post-operative radiotherapy after conservative breast surgery for women with early stage breast cancer

Acronym

TARGIT

Study hypothesis

Current hypothesis as of 17/05/2010:
TARGIT is an international randomised clinical trial designed to test the hypothesis that the strategy of delivering a single dose of targeted intraoperative radiotherapy (IORT) in patients eligible for breast conserving therapy (with the addition of whole breast radiotherapy in those patients at high risk of recurrence elsewhere in the breast [e.g. lobular carcinomas and extensive intraductal component]) is equivalent to a conventional course of post-operative external beam radiotherapy (EBRT). The primary endpoints are local and loco-regional recurrence rates. It is a pragmatic trial in which each participating centre has the option to define more restrictive entry criteria than in the core protocol. Only centres with access to the Intrabeam® (Carl Zeiss) enter patients into the trial. Eligible patients are those with tumours of good prognosis suitable for breast conserving surgery. After giving consent patients are randomised to either IORT or to EBRT. They may receive any other adjuvant treatments as deemed necessary, except for neoadjuvant therapy. The protocol requires that patients be followed at six monthly intervals for five years and then annually.

Previous hypothesis:
The TARGIT trial is an international randomized controlled clinical trial comparing single-day targeted intraoperative radiotherapy to conventional postoperative radiotherapy for women with early stage invasive breast cancer treatable with lumpectomy. Currently, single-day targeted intraoperative radiotherapy is investigational, which means that this treatment is still under evaluation as a treatment for breast cancer. Although small studies indicate that single-day targeted intraoperative radiotherapy is as safe and effective as conventional postoperative radiotherapy for certain patients, a long-term, scientific, head-to-head comparison of the two treatments is needed to determine if they are truly equal. This is the purpose of the TARGIT trial.

Further reading:
More details, including a list of publications, reviews, publicitiy articles, case reports and presentations, can be found at: http://www.dundee.ac.uk/surgery/targit/targitpapers.htm

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/076049
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0007/51892/PRO-07-60-49.pdf

Ethics approval

University College Hospitals Ethics Committee, 25/02/2000, ref: MREC No. 99/0307

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

http://www.dundee.ac.uk/surgery/targit/Dundee%20SIS%20Single%20Procedure%20v2.pdf; http://www.dundee.ac.uk/surgery/targit/Dundee%20SIS%20Subsequent%20Procedure%20v2.pdf

Condition

Breast cancer

Intervention

Current interventions as of 17/05/2010:
Intrabeam device: a dose of 20 Gy at the surface of the applicator or 6 Gy at 1 cm (in water) is prescribed by the radiation oncologist and delivered to the breast tissue. This takes approximately 30 minutes, depending on the size of the applicator.
Post-operative radiotherapy: all patients randomised to receive conventional radiotherapy within this trial should be treated in accordance with a pre-specified policy. Dosage should only be applied to the breast; axillary, supra-clavicular and internal mammary nodes should not generally be irradiated by discrete fields.

Previous interventions:
Use of the Intrabeam device to deliver intra-operative radiotherapy after wide local excision (WLE) as compared to delivery of standard external beam radiotherapy (EBRT).
In the TARGIT trial, half of the participants will receive single-day targeted intraoperative radiotherapy given at the time of surgery. The other half will receive conventional postoperative radiotherapy given over a 6-7 week period beginning after surgery.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

Added 17/05/2010:
Local relapse within the treated breast

Secondary outcome measures

Added 17/05/2010:
1. Site of relapse within the breast
2. Relapse-free survival and overall survival
3. Local toxicity/morbidity

Overall trial start date

01/03/2000

Overall trial end date

31/03/2012

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 17/05/2010:
1. Age 45 years or older
2. Operable invasive breast cancer (T1 and small T2, N0-1, M0) confirmed by cytological or histological examination
3. Suitable for breast conserving surgery
4. Previously diagnosed and treated contralateral breast cancer may be entered but will be randomised to a separate stratum
5. Available for regular follow-up for at least 10 years
Note: Individual centres may wish to restrict entry to a more exactly defined subset of patients, in which case only patients with these characteristics may be entered by that particular centre. For example, centres may decide at outset to recruit only women over 50 or even over 65 years of age. Such policies must be pre-defined in writing and approved by the International Steering Committee.

Previous inclusion criteria:
Eligible patients are those with tumours of good prognosis suitable for breast conserving surgery.

Prior to joining the study, women must meet with the study investigators to determine if they qualify for the TARGIT trial. This evaluation will include a physical examination, review of mammograms and ultrasounds, and review of pathology results. Additional radiology studies (mammograms, ultrasounds, and/or breast MRI) may also be requested prior to determining eligibility for the study.

In order to participate in the TARGIT trial, the following criteria must be met:
1. Age 40 or older
2. Invasive (also called infiltrating) breast cancer
3. Breast cancer measuring 3 cm (1-1/8 in) or less
4. Breast cancer treatable with lumpectomy
5. Capable of receiving breast radiotherapy (not pregnant, no history of previous radiotherapy to the same breast, no connective tissue disorder)

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

3432

Participant exclusion criteria

Current exclusion criteria as of 17/05/2010:
1. More than one obvious cancer in the same breast as diagnosed by clinical examination, mammography or ultrasonography
2. Bilateral breast cancer at the time of diagnosis
3. Ipsilateral breast had a previous cancer and/or irradiation
4. Patients known to have BRCA2 gene mutations, but testing for gene mutations is not required
5. Lobular cancer or extensive intraductal component (EIC ≥25% of the tumour is intraductal) on core biopsy or initial pathology (if performed)
6. Patients undergoing primary medical treatment (hormones or chemotherapy) as initial treatment with neoadjuvant intent of reducing tumour size should be excluded; those given short duration (up to 4 weeks) systemic therapy can be included
7. Patients presenting with gross nodal disease, considered to be clinically malignant or proven cytologically or by scanning. In general, four or more positive nodes or extranodal spread are not suitable for TARGIT alone and should receive EBRT as well. However, individual centres may decide that anything more than micrometastasis should receive EBRT
8. Patients with any severe concomitant disease that may limit their life expectancy
9. Previous history of malignant disease does not preclude entry if the expectation of relapse-free survival at 10 years is 90% or greater
10. Any factor included as exclusion criterion in the local centre's Treatment Policy. This is particularly relevant to patients entered into the post-pathology stratum
11. No more than 30 days can have elapsed between last breast cancer surgery (not axillary) and entry into the trial for patients in the post-pathology stratification

Previous exclusion criteria:
1. Multiple areas of cancer within the breast
2. Cancer in both breasts
3. Diagnostic biopsy shows extensive non-invasive cancer (DCIS or Ductal Carcinoma in Situ)
4. Lymph nodes contain cancer metastasis

Recruitment start date

01/03/2000

Recruitment end date

31/03/2012

Locations

Countries of recruitment

Australia, Canada, Denmark, France, Germany, Italy, Norway, Poland, Switzerland, United Kingdom, United States of America

Trial participating centre

UCL Medical School
London
N19 5LW
United Kingdom

Sponsor information

Organisation

University College London (UK)

Sponsor details

Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2001 pilot study results in: http://www.ncbi.nlm.nih.gov/pubmed/11583188
2. 2002 discussion of operative technique in: http://www.ncbi.nlm.nih.gov/pubmed/12099658
3. 2004 Australian results in: http://www.ncbi.nlm.nih.gov/pubmed/15574144
4. 2005 German results in: http://www.ncbi.nlm.nih.gov/pubmed/16277101
5. 2006 German results on long-term toxicity in: http://www.ncbi.nlm.nih.gov/pubmed/16887294
6. 2006 results on recurrence rates in: http://www.ncbi.nlm.nih.gov/pubmed/17084562
7. 2007 international results in: http://www.ncbi.nlm.nih.gov/pubmed/17826067
8. 2016 environmental and social benefits results in: http://www.ncbi.nlm.nih.gov/pubmed/27160842
9. 2016 results in: https://www.ncbi.nlm.nih.gov/pubmed/27689969

Publication citations

  1. Discussion of operative technique

    Vaidya JS, Baum M, Tobias JS, Morgan S, D'Souza D, The novel technique of delivering targeted intraoperative radiotherapy (Targit) for early breast cancer., Eur J Surg Oncol, 2002, 28, 4, 447-454.

  2. Australian results

    Joseph DJ, Bydder S, Jackson LR, Corica T, Hastrich DJ, Oliver DJ, Minchin DE, Haworth A, Saunders CM, Prospective trial of intraoperative radiation treatment for breast cancer., ANZ J Surg, 2004, 74, 12, 1043-1048, doi: 10.1111/j.1445-1433.2004.03264.x.

  3. German results

    Kraus-Tiefenbacher U, Scheda A, Steil V, Hermann B, Kehrer T, Bauer L, Melchert F, Wenz F, Intraoperative radiotherapy (IORT) for breast cancer using the Intrabeam system., Tumori, 91, 4, 339-345.

  4. Results on recurrence rates

    Vaidya JS, Baum M, Tobias JS, Massarut S, Wenz F, Murphy O, Hilaris B, Houghton J, Saunders C, Corica T, Roncadin M, Kraus-Tiefenbacher U, Melchaert F, Keshtgar M, Sainsbury R, Douek M, Harrison E, Thompson A, Joseph D, Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost., Int. J. Radiat. Oncol. Biol. Phys., 2006, 66, 5, 1335-1338, doi: 10.1016/j.ijrobp.2006.07.1378.

  5. International results

    Holmes DR, Baum M, Joseph D, The TARGIT trial: targeted intraoperative radiation therapy versus conventional postoperative whole-breast radiotherapy after breast-conserving surgery for the management of early-stage invasive breast cancer (a trial update)., Am. J. Surg., 2007, 194, 4, 507-510, doi: 10.1016/j.amjsurg.2007.06.018.

  6. Results

    Vaidya JS, Baum M, Tobias JS, D'Souza DP, Naidu SV, Morgan S, Metaxas M, Harte KJ, Sliski AP, Thomson E, Targeted intra-operative radiotherapy (Targit): an innovative method of treatment for early breast cancer., Ann. Oncol., 2001, 12, 8, 1075-1080.

  7. Results

    Kraus-Tiefenbacher U, Bauer L, Scheda A, Fleckenstein K, Keller A, Herskind C, Steil V, Melchert F, Wenz F, Long-term toxicity of an intraoperative radiotherapy boost using low energy X-rays during breast-conserving surgery., Int. J. Radiat. Oncol. Biol. Phys., 2006, 66, 2, 377-381, doi: 10.1016/j.ijrobp.2006.05.042.

  8. Results

    Coombs NJ, Coombs JM, Vaidya UJ, Singer J, Bulsara M, Tobias JS, Wenz F, Joseph DJ, Brown DA, Rainsbury R, Davidson T, Adamson DJ, Massarut S, Morgan D, Potyka I, Corica T, Falzon M, Williams N, Baum M, Vaidya JS, Environmental and social benefits of the targeted intraoperative radiotherapy for breast cancer: data from UK TARGIT-A trial centres and two UK NHS hospitals offering TARGIT IORT, BMJ Open, 2016 , 6, 5, e010703, doi: 10.1136/bmjopen-2015-010703.

Additional files

Editorial Notes

03/10/2016: Publication reference added. 11/05/2016: Publication reference added. 14/05/2013: Australia, Canada, Denmark, France, Germany, Italy, Norway, Poland, Switzerland, UK and USA were added to the countries of recruitment field. 17/05/2010: the following changes were made to the trial record: 1. The target number of participant was changed from 2400 to 3432. 2. The overall trial start date was changed from 01/08/2004 to 01/03/2000. 3. The overall trial end date was changed from 31/12/2009 to 31/03/2012. 4. The sources of funding field was changed from 'Zeiss Inc (Germany)' to 'NIHR Health Technology Assessment Programme - HTA (UK)'.