Breast CancerTARGIT-CNCT02290782
TARGIT-C(Consolidation) Prospective Phase IV Study of IORT in Patients With Small Breast Cancer
A study testing Intraoperative radiotherapy (IORT) in people with Breast Cancer, run by Universitätsmedizin Mannheim at 4 sites in 2 countries.
Trial summary
This prospective, multicentric single arm phase IV study is based on the protocol of the international TARGIT-A and TARGIT-E study. Patients ≥ 50 years with small, low-risk breast cancer who are operated but not irradiated show local relapse rates around 6% after 5 years. Read more about this study
- Who is it for?
- Ages 50 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Intraoperative radiotherapy (IORT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 387 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Oct 2014to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histologically verified invasive-ductal breast cancer
- hormone receptor positive (if known)
- cT1 or small cT2 (≤ 3.5 cm) cN0 cM0
- ≥ 50 years of age
- informed consent
- compliance
Who cannot join
- extensive intraductal component (EIC)
- negative hormone receptor status
- multifocality /-centricity (mammography, breast ultrasound)
- lymph vessel invasion (L1)
- clinical signs of distant metastases or clinically suspicious lymph nodes
- other histology
Show all 11Show fewer
- < 50 years
- missing informed consent or non-compliance
- bilateral breast cancer at the time of diagnosis
- known BCRA1/2 gene mutations (genetic testing not required)
- any exclusion criterion in the local centre´s treatment policy
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
France2 sites
Institut régional du Cancer de Montpellier
Montpellier, 34298
IUCT, Toulouse
Toulouse
Germany2 sites
Klinikum Kassel
Kassel, 34125
Department of Radiotherapy University Hospital Mannheim
Mannheim, 68167
About this study
Official title: TARGIT-C(Consolidation) Prospective Phase IV Study of Intraoperative Radiotherapy (IORT) in Patients With Small Breast Cancer
This prospective, multicentric single arm phase IV study is based on the protocol of the international TARGIT-A and TARGIT-E study.
Patients ≥ 50 years with small, low-risk breast cancer who are operated but not irradiated show local relapse rates around 6% after 5 years. With adjuvant whole breast radiotherapy (WBRT) the local relapse rate drops to under 1% after 5 years under Tamoxifen (4).
Read more
It has been demonstrated (6, 9, 10) that the efficacy of radiation of the tumor bed only in a selected group can be non-inferior to WBRT.
The TARGIT C study should confirm the efficacy of a single dose of intraoperative radiotherapy (IORT) in a well selected group of patients with small breast cancer and absence of risk factors. In presence of risk factors postoperative WBRT will be added to complete the radiotherapeutic treatment according to international guidelines.
Endpoints are the local relapse rate (within 2 cm of the tumor bed), ipsilateral relapse, cancer-specific and overall survival and contralateral breast cancer as well as documentation of quality of life and cosmetic outcome.
The expected local relapse rates are 0.825/1.375% after 3/5 years, respectively. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 1.55/2.4/4% after 1/3/5 years. Power calculations result in 387 patients with a calculated dropout and loss to follow-up rate of 10%, an alpha of 0.05 and a beta of 0.10. There will be only a pre-pathology stratum.
It is a pragmatic trial in which each participating centre has the option to modify entry criteria and criteria for WBRT according to this core protocol after consultation with the steering committee and local ethics committee (e.g. size, free margins). Only centers with access to the Intrabeam® system (Carl Zeiss) can recruit patients into the trial.
Read the detailed description
- Introduction Randomized studies provide evidence that concerning the overall survival breast conserving surgery (BCS) combined with postoperative radiotherapy is equally effective as modified mastectomy (1, 2, 3). Postoperative radiation decreases the local relapse rate (1, 2) highly significantly in comparison to BCS alone (3). The recent metaanalysis of the Early Breast Cancer Trialists Collaborative Group (EBCTCG (3)) show that the avoidance of 4 local relapses after 5 years can prevent one death in 15 years (4 to 1 rule). Several studies in the past demonstrated that complete omission of radiotherapy failed in terms of local tumor control. Fyles et al. (4) showed local relapse rates of 8% within a low risk group of patients with tumors of pathological stage T1/T2 and >50 years of age treated with BCS and antihormonal treatment (AHT). By adding postoperative whole breast radiation (WBRT) the rate of local relapse was reduced to 1% after 5 years. This effect was also seen in elderly patients with small tumors. Hughes et al. (5) observed low local relapse rates of 4% for patients treated with AHT only after BCS vs. 1% for patients with additional WBRT after 4 years, evaluating a low-risk group of patients with tumors < 2 cm and > 70 years of age. Apparently, all patients benefit from postoperative WBRT. However, due to the fact that 90% of all local relapses after breast conserving therapy are localized very close to the primary tumor, it might be possible to treat a selected group of patients with a relatively low risk of local recurrence with tumor bed irradiation only. Polgar et al. (6) provided evidence of the non-inferiority of accelerated partial breast irradiation (APBI) in comparison to WBRT in a small randomized trial. Very recently the TARGIT-A data (9, 10) reported a non-inferior efficacy of tumor bed irradiation with single dose intraoperative radiation (Intrabeam System, Carl Zeiss Oberkochen) compared to WBRT regarding local relapse. By using the Intrabeam System, the intraoperative radiotherapy (IORT) can be given during surgery with protection of the surrounding tissue while applying a biologically highly effective dose to the tissue adjacent to the tumor. Advantages of IORT are its high precision regarding beam application, its possibility of protection of the skin and the prevention of tumor cell proliferation during the time interval between breast conserving surgery and adjuvant WBRT as well as during fractionated WBRT. By manually positioning of the applicator in the tumor bed geographic miss is excluded and radiation of risk structures like the heart and lung can be avoided. Therefore, it is possible to give a high single fraction to the target and minimize relevant side effects.
- Aim
The objective of this single armed phase IV study is to further investigate the efficacy of a single intraoperative radiotherapy treatment within low risk patients (≥ 50 years, cT1 and small cT2 (< 3.5 cm), cN0, cM0, invasive-ductal, hormone receptor positive) which is followed by WBRT only when risk factors are present.
The primary endpoint is the rate of local relapse (within 2 cm of the initial tumor); secondary endpoints are ipsi- or contralateral breast cancer, cancer specific and overall survival. Of further interest is the cosmetic outcome and Quality of Life.
Therefore, patients ≥ 50 years with small, histologically verified and hormone receptor positive invasive-ductal breast cancer (clinically cT1 or small T2 ≤ 3.5 cm) without risk factors (multifocality/- centricity, extensive intraductal component (EIC), lymph vessel invasion (L1), clinically positive lymph nodes) who receive BCS will be recruited.
After tumor resection with free margins > 1 mm the applicator will be exactly positioned in the tumor bed with a minimum distance to skin of 5 mm. The prescription dose will be 20 Gy to the surface of the applicator. The treatment times depend on the diameter of the applicator and can last up to 20-50 minutes. After radiation the applicator will be removed and the operation finished as usual. The biologic effectiveness of 20 Gy prescribed during the operation is equivalent to 70 Gy normo-fractionated irradiation according to radiobiological modelling.
If the final histopathological report provides evidence of a different histology or risk factors, such as an extensive intraductal component (EIC), lymph vessel invasion (L1), multifocality/-centricity or resection margins <2 mm, patients will receive a postoperative WBRT with 46 Gy (after a delay of at least 5 weeks). Depending on the lymph node status postoperative WBRT will be performed with 50 Gy (pN1) or WBRT including lymphatic drainage with 50 Gy (≥ pN2). A re-resection has to be performed in presence of insufficient free margins (e.g. tumor on ink, or margin < 2mm depending on local policy) and will be followed by WBRT with 50 Gy omitting the boost.
Cosmetic outcome and toxicity evaluation will be performed by chart (CTC and LENT-SOMA score) and standardized photo documentation.
For Quality of Life assessment the patients will complete two standardized and validated questionnaires developed by the EORTC (European Organisation for Research and Treatment of Cancer). The questionnaires include 53 questions and take approximately 10 minutes and will be filled out at clinic visits.
Therefore, a patient group including patients ≥ 50 years with a low-risk tumor profile will be treated in this single-arm study by intraoperative radiotherapy of the tumor bed only, using a well established method (Intrabeam System, Carl Zeiss Surgical, Oberkochen, Germany) in order to optimize radiotherapy treatment after breast conserving surgery in terms of local relapse, toxicity, overall survival and quality of life.
- Conditions
- Breast Cancer
- Being tested
- Intraoperative radiotherapy (IORT)
- Keywords
- toxicity, outcome, TARGIT, quality of life, intraoperative radiotherapy (IORT)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intraoperative radiotherapy (IORT)Radiation
The surgeon and radiation oncologist should choose the largest possible suitable applicator in order to ensure that the highest possible dose is delivered to the tumor bed tissue. A dose of 20 Gy at the surface of the applicator (in water) is prescribed by the radiation oncologist and delivered to the breast tissue. This takes approximately 20-50 minutes, depending on the size of the applicator.
To minimize radiation dependent side effects the skin-applicator surface distance should be more than 5 mm.
| Study group | Role | What they receive |
|---|---|---|
| Intraoperative radiotherapy (IORT) | Experimental | IORT (20Gy) as intervention will be given during breast conserving surgery. If risk factors (Tumor > 3.5 cm, lobular cancer, resection margin < 2 mm*, L1, pN+ mulitfocal/multicentric, EIC, negative hormone receptors) are present, external beam radiotherapy will be added.
* In case of positive margins (<2 mm resection margin) a re-resection should be done Receives: Radiation: Intraoperative radiotherapy (IORT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local relapse
Local relapse rate within 2 cm of the tumor bed
Measured: 5 years
Secondary outcomes (4)
Ipsi- or contralateral breast cancer
Ipsi- or contralateral breast cancer
Measured: 5 years
Survival
Breast cancer related and overall survival
Measured: 5 years
Toxicity (CTC, LENT SOMA)
Cosmetic outcome, acute and late toxicity measured by CTC Score V5 and LENT SOMA scale (fibrosis, telangiectasia, edema arm, edema breast, ulceration, hyperpigmentation, pain, retraction
Measured: 5 years
General QoL and breast specific QoL (EORTC QLQ C30 + BR23)
measured by EORTC QLQ C30 and BR23 questionnaires; longitudinal analysis
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm study: IORT +/- EBRT (risk adapted approach).
- Masking
- None (open label)
- Enrolment
- 387 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsmedizin Mannheim
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elena Sperk, MD, Universitätsmedizin Mannheim
- Investigators
- Elena Sperk, MD, Principal investigator, department of radiation oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02290782
- Sponsor's protocol ID
- TARGIT C
- Acronym
- TARGIT-C
- Status last verified
- Mar 2025
- First submitted
- 30 Oct 2014
- Last updated
- 26 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995 Nov 30;333(22):1456-61. doi: 10.1056/NEJM199511303332203.
PubMed 7477145Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002 Oct 17;347(16):1227-32. doi: 10.1056/NEJMoa020989.
PubMed 12393819Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0.
PubMed 15894097Fyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, Weir LM, Olivotto IA. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):963-70. doi: 10.1056/NEJMoa040595.
PubMed 15342804Hughes KS, Schnaper LA, Berry D, Cirrincione C, McCormick B, Shank B, Wheeler J, Champion LA, Smith TJ, Smith BL, Shapiro C, Muss HB, Winer E, Hudis C, Wood W, Sugarbaker D, Henderson IC, Norton L; Cancer and Leukemia Group B; Radiation Therapy Oncology Group; Eastern Cooperative Oncology Group. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):971-7. doi: 10.1056/NEJMoa040587.
PubMed 15342805Polgar C, Fodor J, Major T, Nemeth G, Lovey K, Orosz Z, Sulyok Z, Takacsi-Nagy Z, Kasler M. Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma--5-year results of a randomized trial. Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):694-702. doi: 10.1016/j.ijrobp.2007.04.022. Epub 2007 May 25.
PubMed 17531400Kraus-Tiefenbacher U, Bauer L, Kehrer T, Hermann B, Melchert F, Wenz F. Intraoperative radiotherapy (IORT) as a boost in patients with early-stage breast cancer -- acute toxicity. Onkologie. 2006 Mar;29(3):77-82. doi: 10.1159/000091160. Epub 2006 Mar 3.
PubMed 16514267Kraus-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 Oct 1;66(2):377-81. doi: 10.1016/j.ijrobp.2006.05.042. Epub 2006 Aug 2.
PubMed 16887294Vaidya 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.
PubMed 20570343Vaidya 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.
PubMed 24224997Vaidya 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.
PubMed 32816842
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TARGIT-C(Consolidation) Prospective Phase IV Study of Intraoperative Radiotherapy (IORT) in Patients With Small Breast Cancer
- ClinicalTrials.gov ID
- NCT02290782
- Acronym / sponsor ID
- TARGIT-C / TARGIT C
- Conditions
- Breast Cancer
- Keywords
- toxicity, outcome, TARGIT, quality of life, intraoperative radiotherapy (IORT)
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 387 participants (actual)
- Lead sponsor
- Universitätsmedizin MannheimUniversity, hospital or other
- Study start
- Oct 2014 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 14 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This prospective, multicentric single arm phase IV study is based on the protocol of the international TARGIT-A and TARGIT-E study.
Patients ≥ 50 years with small, low-risk breast cancer who are operated but not irradiated show local relapse rates around 6% after 5 years. With adjuvant whole breast radiotherapy (WBRT) the local relapse rate drops to under 1% after 5 years under Tamoxifen (4).
It has been demonstrated (6, 9, 10) that the efficacy of radiation of the tumor bed only in a selected group can be non-inferior to WBRT.
The TARGIT C study should confirm the efficacy of a single dose of intraoperative radiotherapy (IORT) in a well selected group of patients with small breast cancer and absence of risk factors. In presence of risk factors postoperative WBRT will be added to complete the radiotherapeutic treatment according to international guidelines.
Endpoints are the local relapse rate (within 2 cm of the tumor bed), ipsilateral relapse, cancer-specific and overall survival and contralateral breast cancer as well as documentation of quality of life and cosmetic outcome.
The expected local relapse rates are 0.825/1.375% after 3/5 years, respectively. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 1.55/2.4/4% after 1/3/5 years. Power calculations result in 387 patients with a calculated dropout and loss to follow-up rate of 10%, an alpha of 0.05 and a beta of 0.10. There will be only a pre-pathology stratum.
It is a pragmatic trial in which each participating centre has the option to modify entry criteria and criteria for WBRT according to this core protocol after consultation with the steering committee and local ethics committee (e.g. size, free margins). Only centers with access to the Intrabeam® system (Carl Zeiss) can recruit patients into the trial.
Detailed description
- Introduction Randomized studies provide evidence that concerning the overall survival breast conserving surgery (BCS) combined with postoperative radiotherapy is equally effective as modified mastectomy (1, 2, 3). Postoperative radiation decreases the local relapse rate (1, 2) highly significantly in comparison to BCS alone (3). The recent metaanalysis of the Early Breast Cancer Trialists Collaborative Group (EBCTCG (3)) show that the avoidance of 4 local relapses after 5 years can prevent one death in 15 years (4 to 1 rule). Several studies in the past demonstrated that complete omission of radiotherapy failed in terms of local tumor control. Fyles et al. (4) showed local relapse rates of 8% within a low risk group of patients with tumors of pathological stage T1/T2 and >50 years of age treated with BCS and antihormonal treatment (AHT). By adding postoperative whole breast radiation (WBRT) the rate of local relapse was reduced to 1% after 5 years. This effect was also seen in elderly patients with small tumors. Hughes et al. (5) observed low local relapse rates of 4% for patients treated with AHT only after BCS vs. 1% for patients with additional WBRT after 4 years, evaluating a low-risk group of patients with tumors < 2 cm and > 70 years of age. Apparently, all patients benefit from postoperative WBRT. However, due to the fact that 90% of all local relapses after breast conserving therapy are localized very close to the primary tumor, it might be possible to treat a selected group of patients with a relatively low risk of local recurrence with tumor bed irradiation only. Polgar et al. (6) provided evidence of the non-inferiority of accelerated partial breast irradiation (APBI) in comparison to WBRT in a small randomized trial. Very recently the TARGIT-A data (9, 10) reported a non-inferior efficacy of tumor bed irradiation with single dose intraoperative radiation (Intrabeam System, Carl Zeiss Oberkochen) compared to WBRT regarding local relapse. By using the Intrabeam System, the intraoperative radiotherapy (IORT) can be given during surgery with protection of the surrounding tissue while applying a biologically highly effective dose to the tissue adjacent to the tumor. Advantages of IORT are its high precision regarding beam application, its possibility of protection of the skin and the prevention of tumor cell proliferation during the time interval between breast conserving surgery and adjuvant WBRT as well as during fractionated WBRT. By manually positioning of the applicator in the tumor bed geographic miss is excluded and radiation of risk structures like the heart and lung can be avoided. Therefore, it is possible to give a high single fraction to the target and minimize relevant side effects.
- Aim
The objective of this single armed phase IV study is to further investigate the efficacy of a single intraoperative radiotherapy treatment within low risk patients (≥ 50 years, cT1 and small cT2 (< 3.5 cm), cN0, cM0, invasive-ductal, hormone receptor positive) which is followed by WBRT only when risk factors are present.
The primary endpoint is the rate of local relapse (within 2 cm of the initial tumor); secondary endpoints are ipsi- or contralateral breast cancer, cancer specific and overall survival. Of further interest is the cosmetic outcome and Quality of Life.
Therefore, patients ≥ 50 years with small, histologically verified and hormone receptor positive invasive-ductal breast cancer (clinically cT1 or small T2 ≤ 3.5 cm) without risk factors (multifocality/- centricity, extensive intraductal component (EIC), lymph vessel invasion (L1), clinically positive lymph nodes) who receive BCS will be recruited.
After tumor resection with free margins > 1 mm the applicator will be exactly positioned in the tumor bed with a minimum distance to skin of 5 mm. The prescription dose will be 20 Gy to the surface of the applicator. The treatment times depend on the diameter of the applicator and can last up to 20-50 minutes. After radiation the applicator will be removed and the operation finished as usual. The biologic effectiveness of 20 Gy prescribed during the operation is equivalent to 70 Gy normo-fractionated irradiation according to radiobiological modelling.
If the final histopathological report provides evidence of a different histology or risk factors, such as an extensive intraductal component (EIC), lymph vessel invasion (L1), multifocality/-centricity or resection margins <2 mm, patients will receive a postoperative WBRT with 46 Gy (after a delay of at least 5 weeks). Depending on the lymph node status postoperative WBRT will be performed with 50 Gy (pN1) or WBRT including lymphatic drainage with 50 Gy (≥ pN2). A re-resection has to be performed in presence of insufficient free margins (e.g. tumor on ink, or margin < 2mm depending on local policy) and will be followed by WBRT with 50 Gy omitting the boost.
Cosmetic outcome and toxicity evaluation will be performed by chart (CTC and LENT-SOMA score) and standardized photo documentation.
For Quality of Life assessment the patients will complete two standardized and validated questionnaires developed by the EORTC (European Organisation for Research and Treatment of Cancer). The questionnaires include 53 questions and take approximately 10 minutes and will be filled out at clinic visits.
Therefore, a patient group including patients ≥ 50 years with a low-risk tumor profile will be treated in this single-arm study by intraoperative radiotherapy of the tumor bed only, using a well established method (Intrabeam System, Carl Zeiss Surgical, Oberkochen, Germany) in order to optimize radiotherapy treatment after breast conserving surgery in terms of local relapse, toxicity, overall survival and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm study: IORT +/- EBRT (risk adapted approach).
| Arm | Type | Receives |
|---|---|---|
| Intraoperative radiotherapy (IORT) | Experimental | Radiation: Intraoperative radiotherapy (IORT)IORT (20Gy) as intervention will be given during breast conserving surgery. If risk factors (Tumor > 3.5 cm, lobular cancer, resection margin < 2 mm*, L1, pN+ mulitfocal/multicentric, EIC, negative hormone receptors) are present, external beam radiotherapy will be added. * In case of positive margins (<2 mm resection margin) a re-resection should be done |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- histologically verified invasive-ductal breast cancer
- hormone receptor positive (if known)
- cT1 or small cT2 (≤ 3.5 cm) cN0 cM0
- ≥ 50 years of age
- informed consent
Key exclusion criteria (11 listed)
- extensive intraductal component (EIC)
- negative hormone receptor status
- multifocality /-centricity (mammography, breast ultrasound)
- lymph vessel invasion (L1)
- clinical signs of distant metastases or clinically suspicious lymph nodes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intraoperative radiotherapy (IORT)The surgeon and radiation oncologist should choose the largest possible suitable applicator in order to ensure that the highest possible dose is delivered to the tumor bed tissue. A dose of 20 Gy at the surface of the applicator (in water) is prescribed by the radiation oncologist and delivered to the breast tissue. This takes approximately 20-50 minutes, depending on the size of the applicator. To minimize radiation dependent side effects the skin-applicator surface distance should be more than 5 mm. | Radiation | Intraoperative radiotherapy (IORT) |
Primary outcome
Local relapse
Time frame: 5 years
Local relapse rate within 2 cm of the tumor bed
4 secondary outcomes
Ipsi- or contralateral breast cancer
Time frame: 5 years
Survival
Time frame: 5 years
Toxicity (CTC, LENT SOMA)
Time frame: 5 years
General QoL and breast specific QoL (EORTC QLQ C30 + BR23)
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Background: PubMed 7477145Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995 Nov 30;333(22):1456-61. doi: 10.1056/NEJM199511303332203.
- Background: PubMed 12393819Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002 Oct 17;347(16):1227-32. doi: 10.1056/NEJMoa020989.
- Background: PubMed 15894097Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0.
- Background: PubMed 15342804Fyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, Weir LM, Olivotto IA. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):963-70. doi: 10.1056/NEJMoa040595.
- Background: PubMed 15342805Hughes KS, Schnaper LA, Berry D, Cirrincione C, McCormick B, Shank B, Wheeler J, Champion LA, Smith TJ, Smith BL, Shapiro C, Muss HB, Winer E, Hudis C, Wood W, Sugarbaker D, Henderson IC, Norton L; Cancer and Leukemia Group B; Radiation Therapy Oncology Group; Eastern Cooperative Oncology Group. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):971-7. doi: 10.1056/NEJMoa040587.
- Background: PubMed 17531400Polgar C, Fodor J, Major T, Nemeth G, Lovey K, Orosz Z, Sulyok Z, Takacsi-Nagy Z, Kasler M. Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma--5-year results of a randomized trial. Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):694-702. doi: 10.1016/j.ijrobp.2007.04.022. Epub 2007 May 25.
- Background: PubMed 16514267Kraus-Tiefenbacher U, Bauer L, Kehrer T, Hermann B, Melchert F, Wenz F. Intraoperative radiotherapy (IORT) as a boost in patients with early-stage breast cancer -- acute toxicity. Onkologie. 2006 Mar;29(3):77-82. doi: 10.1159/000091160. Epub 2006 Mar 3.
- Background: PubMed 16887294Kraus-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 Oct 1;66(2):377-81. doi: 10.1016/j.ijrobp.2006.05.042. Epub 2006 Aug 2.
- Background: PubMed 20570343Vaidya 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.
- Background: PubMed 24224997Vaidya 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.
- Background: PubMed 32816842Vaidya 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elena Sperk, MD principal investigator
department of radiation oncology
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intraoperative radiotherapy (IORT) in people with Breast Cancer, run by Universitätsmedizin Mannheim at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local relapse (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02290782, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2025.