Clinical trial NCT00983684: Comparison of Intra-operative Radiotherapy With Post-operative Radiotherapy for Women With Early Breast Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Invasive Breast Cancer
Breast Cancer
Keywords: Neoplasms by Site
Breast Neoplasms
Breast Diseases
Breast Cancer
Cancer of Breast
Cancer of the Breast
Carcinoma
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2009-09-24
Enrollment: 3451
Sex: FEMALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether a single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence is equivalent to standard post-operative external beam radiotherapy after breast conserving surgery in women with early stage breast cancer in terms of local relapse within the treated breast.

Detailed description: 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.

Eligibility criteria: Inclusion criteria

* Age 45 years or older
* Operable invasive breast cancer (T1 and small T2, N0-1, M0) confirmed by cytological or histological examination
* Suitable for breast conserving surgery
* Previously diagnosed and treated contralateral breast cancer may be entered but will be randomised to a separate stratum.
* Available for regular follow-up for at least ten 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.

Exclusion criteria

* More than one obvious cancer in the same breast as diagnosed by clinical examination, mammography or ultrasonography.
* Bilateral breast cancer at the time of diagnosis.
* Ipsilateral breast had a previous cancer and/or irradiation.
* Patients known to have BRCA2 gene mutations, but testing for gene mutations is not required
* Lobular cancer or Extensive intraductal Component (EIC =\>25% of the tumour is intraductal) on core biopsy or initial pathology (if performed)
* 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.
* Patients presenting with gross nodal disease, considered to be clinically malignant or proven cytologically or by scanning. In general, 4 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.
* Patients with any severe concomitant disease that may limit their life expectancy.
* Previous history of malignant disease does not preclude entry if the expectation of relapse-free survival at 10 years is 90% or greater.
* 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.
* 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.

Primary outcomes:
measure: Local relapse within the treated breast.
timeFrame: 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108, 120 months
Secondary outcomes:
measure: Site of relapse within the breast
timeFrame: 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108, 120 months
measure: Relapse-free survival and overall survival
timeFrame: 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108, 120 months
measure: Local toxicity/morbidity
timeFrame: 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108, 120 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Clinical Trials Group
Study officials:
affiliation: University College London Hospitals
name: Jeffrey S Tobias, MD FRCP FRCR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eiermann W, Keshtgar M, Dewar J, Kraus-Tiefenbacher U, Sutterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet. 2010 Jul 10;376(9735):91-102. doi: 10.1016/S0140-6736(10)60837-9.
citation: Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, Flyger HL, Massarut S, Alvarado M, Saunders C, Eiermann W, Metaxas M, Sperk E, Sutterlin M, Brown D, Esserman L, Roncadin M, Thompson A, Dewar JA, Holtveg HM, Pigorsch S, Falzon M, Harris E, Matthews A, Brew-Graves C, Potyka I, Corica T, Williams NR, Baum M; TARGIT trialists' group. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014 Feb 15;383(9917):603-13. doi: 10.1016/S0140-6736(13)61950-9. Epub 2013 Nov 11.
citation: Vaidya JS, Bulsara M, Baum M, Wenz F, Massarut S, Pigorsch S, Alvarado M, Douek M, Saunders C, Flyger H, Eiermann W, Brew-Graves C, Williams NR, Potyka I, Roberts N, Bernstein M, Brown D, Sperk E, Laws S, Sutterlin M, Corica T, Lundgren S, Holmes D, Vinante L, Bozza F, Pazos M, Blanc-Onfroy ML, Gruber G, Polkowski W, Dedes KJ, Niewald M, Blohmer J, McReady D, Hoefer R, Kelemen P, Petralia G, Falzon M, Joseph D, Tobias JS. New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer. Br J Cancer. 2021 Aug;125(3):380-389. doi: 10.1038/s41416-021-01440-8. Epub 2021 May 25.
citation: Vaidya JS, Bulsara M, Baum M, Wenz F, Massarut S, Pigorsch S, Alvarado M, Douek M, Saunders C, Flyger HL, Eiermann W, Brew-Graves C, Williams NR, Potyka I, Roberts N, Bernstein M, Brown D, Sperk E, Laws S, Sutterlin M, Corica T, Lundgren S, Holmes D, Vinante L, Bozza F, Pazos M, Le Blanc-Onfroy M, Gruber G, Polkowski W, Dedes KJ, Niewald M, Blohmer J, McCready D, Hoefer R, Kelemen P, Petralia G, Falzon M, Joseph DJ, Tobias JS. Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial. BMJ. 2020 Aug 19;370:m2836. doi: 10.1136/bmj.m2836.
citation: Vaidya JS, Bulsara M, Saunders C, Flyger H, Tobias JS, Corica T, Massarut S, Wenz F, Pigorsch S, Alvarado M, Douek M, Eiermann W, Brew-Graves C, Williams N, Potyka I, Roberts N, Bernstein M, Brown D, Sperk E, Laws S, Sutterlin M, Lundgren S, Holmes D, Vinante L, Bozza F, Pazos M, Le Blanc-Onfroy M, Gruber G, Polkowski W, Dedes KJ, Niewald M, Blohmer J, McCready D, Hoefer R, Kelemen P, Petralia G, Falzon M, Baum M, Joseph D. Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer. JAMA Oncol. 2020 Jul 1;6(7):e200249. doi: 10.1001/jamaoncol.2020.0249. Epub 2020 Jul 9.
citation: Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Saunders C, Brew-Graves C, Potyka I, Morris S, Vaidya HJ, Williams NR, Baum M. An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial). Health Technol Assess. 2016 Sep;20(73):1-188. doi: 10.3310/hta20730.