TARGIT-C(Consolidation) Prospective Phase IV Study of IORT in Patients With Small Breast Cancer

NCT02290782 | Active Not Recruiting

• 1 other identifier: TARGIT C
• Study Type: interventional
• Target: 387
• Locations: 2 countries
• Sites: 4

Brief 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. 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.

Conditions

Breast Cancer

Keywords

toxicity; outcome; TARGIT; quality of life; intraoperative radiotherapy (IORT)

Outcome Measures

Primary Outcomes (1)

• Local relapse

  Local relapse rate within 2 cm of the tumor bed

  5 years

Secondary Outcomes (4)

• Ipsi- or contralateral breast cancer

  5 years

• Survival

  5 years

• Toxicity (CTC, LENT SOMA)

  5 years

• General QoL and breast specific QoL (EORTC QLQ C30 + BR23)

  5 years

Study Arms (1)

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

Radiation: Intraoperative radiotherapy (IORT)

Interventions

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.

Intraoperative radiotherapy (IORT)

Eligibility Criteria

• Age: 50 Years+
• Gender Eligibility Details: breast cancer in females
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• \< 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)

Sponsors & Collaborators

• Universitätsmedizin Mannheim: lead

Study Sites (4)

Institut régional du Cancer de Montpellier

Montpellier, 34298, France

Location

IUCT, Toulouse

Toulouse, France

Location

Klinikum Kassel

Kassel, 34125, Germany

Location

Department of Radiotherapy University Hospital Mannheim

Mannheim, 68167, Germany

Location

Related Publications (11)

• 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.

  PMID: 7477145 BACKGROUND

• Veronesi 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.

  PMID: 12393819 BACKGROUND

• Early 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.

  PMID: 15894097 BACKGROUND

• Fyles 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.

  PMID: 15342804 BACKGROUND

• Hughes 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.

  PMID: 15342805 BACKGROUND

• Polgar 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.

  PMID: 17531400 BACKGROUND

• Kraus-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.

  PMID: 16514267 BACKGROUND

• 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 Oct 1;66(2):377-81. doi: 10.1016/j.ijrobp.2006.05.042. Epub 2006 Aug 2.

  PMID: 16887294 BACKGROUND

• 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.

  PMID: 20570343 BACKGROUND

• 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.

  PMID: 24224997 BACKGROUND

• 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.

  PMID: 32816842 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Elena Sperk, MD

  department of radiation oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Clinical Trials Unit, Department of Radiation Oncology Mannheim

Model Details: Single arm study: IORT +/- EBRT (risk adapted approach).

Study Record Dates

• First Submitted: October 30, 2014
• First Posted: November 14, 2014
• Study Start: October 1, 2014
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 26, 2025

Record last verified: 2025-03

Locations

FR (2); DE (2)