Breast CancerNCT07020780

5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics

A study testing Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed in people with Breast Cancer, run by IRCCS San Raffaele at 1 site in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial summary

This is a prospective, randomized, single-center, non-inferiority interventional clinical trial comparing whole breast irradiation (WBI) to a total dose of 26 Gy in 5 fractions with simultaneous integrated boost (SIB) to the tumor bed to a total dose of 30 Gy, and WBI to a total dose of 40.05 Gy in 15 fractions with… Read more about this study

Who is it for?: Ages 18 to 70 years, women only
Conditions the study is for: Breast Cancer
What is being tested?: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 458 participants
Where: 1 siteItaly
Study dates: 25 Jul 2025to 30 Jun 2035
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 18 to 70 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Histological diagnosis of breast cancer
Patients younger than 40 years regardless of histological subtype, or patients between 40 and 70 years with lobular carcinoma, histological subtypes Luminal B Her2 positive, or with hormone receptors negative and Her2 positive (ErbB2), or triple negative (TNBC)
Signed informed consent
Clinical stage T1-T3, Nx-N3
Negative surgical margins (≥ 0.2 cm)
Clinical M0 in the previous 3 months

Show all 9Show fewer

PS (ECOG) ≤2
No previous thoracic radiotherapy
Fertile women using contraceptive methods started during oncological treatment

Who cannot join

Patients with favorable characteristics (Luminal A, Luminal B Her2 negative, ≥ 40 years) undergoing partial irradiation
Patients who have undergone mastectomy
Multicentric tumors
Positive or close surgical margins (<0.2 cm)
BRCA1/2 positive (only if known)
Serious systemic diseases

Show all 13Show fewer

Mental or other disorders that may prevent the patient from signing the informed consent
Previous invasive tumor, except skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (for example carcinoma in situ of the oral cavity or bladder)
Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome)
Evidence of distant metastases (M1)
Contraindication to treatment systemic
Pregnant women
Non-compliance with the dose limits established in the treatment plan

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Andrei Fodor, MD contact

+390226437634

fodor.andrei@hsr.it

Roberta Tummineri, MD contact

+390226435452

tummineri.roberta@hsr.it

Italy1 site, 1 recruiting

IRCCS San Raffaele Scientific Institute
Milan, 20132
Andrei Fodor, MD, +390226437634, fodor.andrei@hsr.it
Roberta G Tummineri, MD, +390226435452, tummineri.roberta@hsr.it
Recruiting

Other trials in Italy

About this study

Official title: Five Fractions Ultrahypofractionated Whole Breast Radiotherapy and Simultaneous Integrated Boost to the Tumor Bed, for Breast Cancer Patients With Unfavorable Characteristics

Read the detailed description

The project refers to a study on patients with T1-T3 Nx-N3 breast cancer, aged under 40 years or with unfavorable histology (lobular carcinoma, multifocal tumor, or histological subtypes Luminal B Her2 positive, Hormonal Receptors negative Her 2 positive, Triple Negative Breast Cancer-TNBC-) treated with breast-conserving surgery (BCS) and radiotherapy to the whole breast (+/- lymph node areas) to a total dose of 26 Gy in 5 fractions, with simultaneous boost (SIB) to the tumor bed to the total dose of 30 Gy, that will be compared with the current departmental standard of moderately hypofractionated radiotherapy to the whole breast, to 40.05 Gy in 15 fractions, with SIB to the tumor bed to a total dose of 48 Gy.

Conditions: Breast Cancer
Being tested: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed
Keywords: Breast Cancer, Whole Breast Irradiation, Simultaneous Integrated Boost, Adjuvant Radiotherapy, Utrahypofractionated Radiotherapy, Moderately Hypofractionated Radiotherapy
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bedRadiation
Also called Ultrahypofractionated WBI with SIB
Experimental arm (arm 1-five fractions WBI) patients will be treated to a total dose (TD) of 26 Gy in 5 fractions to whole breast, and a simultaneous integrated boost (SIB) to a TD of 30 Gy to the tumor bed, while arm 2-fifteen-fractions WBI patients with 40 Gy/15 fractions to PTV, and 48 Gy SIB to the tumor bed.

Study groups in NCT07020780
Study group	Role	What they receive
Arm 1- Five fractions radiotherapy	Experimental	Patients in the study (randomized to arm 1) will be treated to the whole breast to a total dose (TD) of 26 Gy in 5 fractions, with simultaneous integrated boost (SIB) to a TD of 30 Gy to the tumor bed. For each patient, an IMRT (intensity modulated radiotherapy) treatment plan will be created to ensure adequate coverage of the treatment volumes and the tolerability of the Organs At Risk (OAR). Specific, already validated dose-volume constraints will be applied for the evaluation of OARs. The dose-volume histogram (DVH) for the Gross Tumor Volume (GTV), Clinical Target Volume (CTV), PTV, and OAR will be calculated in order to achieve the best optimization in terms of tolerability and efficacy. Receives: Radiation: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed
Arm 2- Fifteen fractions radiotherapy	Active comparator	Patients randomized to arm 2 will be treated according to the standard protocol of our department, delivering adjuvant whole breast irradiation (WBI) to a total dose (TD) of 40.05 Gy in 15 fractions, with simultaneous integrated boost (SIB) to the tumor bed to a TD of 48 Gy. Receives: Radiation: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed

What is being measured

The primary outcome is the main question the study is designed to answer.

Local Relapse Free Survival (LRFS)
- demonstrate the non-inferiority of local control (local relapse free survival - LRFS) of the study treatment (delivered in five fractions) compared to the department's standard WBI treatment (delivered in 15 fractions).
Measured: 5 years

Secondary outcomes (21)

Acute toxicity
Acute toxicity grade ≥3 as the maximum toxicity value within 1 month and 3 months after the completion of radiotherapy treatment evaluated with RTOG/EORTC scale with 4 grades, from 0 no change to 4, worst toxicity
Measured: 1 month
Acute toxicity
Acute toxicity grade ≥3 as the maximum toxicity value within 1 month and 3 months after the completion of radiotherapy treatment evaluated with RTOG/EORTC scale with 4 grades, from 0 no change to 4, worst toxicity
Measured: 3 months
Late RTOG toxicity
Late skin toxicity evaluated with RTOG/EORTC scale, with 4 grades, from 0 = no change, to 4 = maximum toxicity
Measured: 5 years
Late CTCAE toxicity
Late toxicity evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale, with 5 grades, from 0 = no change, to 5 = death for toxicity
Measured: 5 years
Local Control
Local control of the treated site expressed in terms of local recurrence rate
Measured: 5 years
Ipsilateral Breast Tumor Recurrence (IBTR)
Ipsilateral breast tumor recurrence - IBTR- of the study treatment (delivered in 5 fractions WBI+SIB) compared to the department's standard WBI+SIB treatment (delivered in 15 fractions).
Measured: 5 years
Regional Relapse-Free Survival (RRFS)
Time to regional (nodal) recurrence
Measured: From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years
Distant Metastasis-Free Survival (DMFS)
Time to distant (metastatic) relapse
Measured: From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years
Disease-Free Survival (DFS)
Time to first any relapse: local, regional or distant
Measured: From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years
Breast Cancer Specific Survival (BCSS)
Time until death from breast cancer
Measured: From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years
Overall Survival (OS)
Time until death from any cause
Measured: From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years
Cosmesis
Cosmetic results evaluated with Harvard scale. It assesses the global esthetic appearance of the breast, categorized as Excellent, Good, Fair, or Poor
Measured: 5 years
Acute toxicity interim analysis
An interim analysis of acute toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 200 patients
Measured: 3 months
Late toxicity interim analysis
An interim analysis of late toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 200 patients
Measured: 42 months
Local relapse interim analysis
An interim analysis of local relapse rate will be performed for the first 200 patients
Measured: 42 months
Incidence of Treatment-Emergent Adverse Events as assessed with breast tumor specific quality of life questionnaires
Survey with the questionnaire of European Organisation for Research and Treatment of Cancer (EORTC) Quality of life of brain tumor patients (EORTC QLQ BR42) which contains 42 questions on patients' quality of life with answers from 1, lowest grade, to 4, highest grade
Measured: 5 years
Modeling of organ movement
Modeling of organ movement during treatment
Measured: 15 days
Radiomics
CT radiomic features predicting relapse or death will be extracted, acording to IBSI (Image Biomarker Standardisation Initiative), owning to the different families of features: Morphology, Statistical, Intensity Histogram, Grey Level Cooccurrence Matrix 3D-average, Grey Level Co-occurrence Matrix 3D-combined, Grey Level Run Lenght 3D-average. Grey Level Run Lenght 3D_combined, Grey Level Size Zone Matrix 3D, Neighbors Grey Tone Difference Matrix 3D, Grey Level Distance Zone Matrix 3D, standard convolutional filters within radiomic workflow (wavelets, Laplacian of Gaussian). Area Under Curve (AUC) will be taken as representative of the discriminative power for each of the significant RF.
Measured: 5 years
Predictive factors for toxicity
Identification of clinical, imaging, and laboratory prognostic factors for toxicity. Univariable and multivariable Cox analysis will be performed to identify factors associated with >/= G2 toxicity
Measured: 5 years
Predictive factors for disease progression
Identification of clinical, imaging, and laboratory prognostic factors for an aggressive phenotype of breast cancer. Univariable and multivariable analysis will be performed to identify factors associated with disease progression
Measured: 5 years
Predictive factors for death
Identification of clinical, imaging, and laboratory prognostic factors for an aggressive phenotype of breast cancer. Univariable and multivariable Cox analysis will be performed to identify factors associated with death.
Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Jul 202530 Jun 2035

First posted13 Jun 2025
Study start25 Jul 2025
Primary completion30 Jun 2029 (estimated)
Study completion30 Jun 2035 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (45)Papers the sponsor has linked to this study.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
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: Randomised
Intervention model: Parallel groups
Model description: A total of 458 patients are expected to be enrolled in this prospective, randomized study. A power of 80% and a significance level α of 5% are used to calculate the sample size. The hypothesis is that the proportion of patients free from local recurrence 5 years after the end of treatment is not less than 95.4%, with a margin of 5%. A total of 218 patients per arm are needed, and an additional 5% (22 patients) to compensate for dropouts.
Masking: None (open label)
Enrolment: 458 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07020780
Sponsor's protocol ID: HY FIVE
Status last verified: Oct 2026
First submitted: 27 May 2025
Last updated: 22 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: The data that support the findings of this study (anonymized individual participant data) are available on request from the corresponding author to researchers who provide a methodologically sound proposal. Requests made to the corresponding author will be evaluated by the Lombardy Territorial Ethics Committee 1

Publications

START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008 Mar 29;371(9618):1098-107. doi: 10.1016/S0140-6736(08)60348-7. Epub 2008 Mar 19.
PubMed 18355913
Clark RM, Whelan T, Levine M, Roberts R, Willan A, McCulloch P, Lipa M, Wilkinson RH, Mahoney LJ. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group. J Natl Cancer Inst. 1996 Nov 20;88(22):1659-64. doi: 10.1093/jnci/88.22.1659.
PubMed 8931610
Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, Shelley W, Grimard L, Bowen J, Lukka H, Perera F, Fyles A, Schneider K, Gulavita S, Freeman C. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010 Feb 11;362(6):513-20. doi: 10.1056/NEJMoa0906260.
PubMed 20147717
Shaitelman SF, Lei X, Thompson A, Schlembach P, Bloom ES, Arzu IY, Buchholz D, Chronowski G, Dvorak T, Grade E, Hoffman K, Perkins G, Reed VK, Shah SJ, Stauder MC, Strom EA, Tereffe W, Woodward WA, Amaya DN, Shen Y, Hortobagyi GN, Hunt KK, Buchholz TA, Smith BD. Three-Year Outcomes With Hypofractionated Versus Conventionally Fractionated Whole-Breast Irradiation: Results of a Randomized, Noninferiority Clinical Trial. J Clin Oncol. 2018 Oct 31;36(35):JCO1800317. doi: 10.1200/JCO.18.00317. Online ahead of print.
PubMed 30379626
Chua BH, Link EK, Kunkler IH, Whelan TJ, Westenberg AH, Gruber G, Bryant G, Ahern V, Purohit K, Graham PH, Akra M, McArdle O, O'Brien P, Harvey JA, Kirkove C, Maduro JH, Campbell ID, Delaney GP, Martin JD, Vu TTT, Muanza TM, Neal A, Olivotto IA; BIG 3-07/TROG 07.01 trial investigators. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study. Lancet. 2022 Aug 6;400(10350):431-440. doi: 10.1016/S0140-6736(22)01246-6.
PubMed 35934006
Meattini I, Becherini C, Boersma L, Kaidar-Person O, Marta GN, Montero A, Offersen BV, Aznar MC, Belka C, Brunt AM, Dicuonzo S, Franco P, Krause M, MacKenzie M, Marinko T, Marrazzo L, Ratosa I, Scholten A, Senkus E, Stobart H, Poortmans P, Coles CE. European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer. Lancet Oncol. 2022 Jan;23(1):e21-e31. doi: 10.1016/S1470-2045(21)00539-8.
PubMed 34973228
Marta GN, Coles C, Kaidar-Person O, Meattini I, Hijal T, Zissiadis Y, Pignol JP, Ramiah D, Ho AY, Cheng SH, Sancho G, Offersen BV, Poortmans P. The use of moderately hypofractionated post-operative radiation therapy for breast cancer in clinical practice: A critical review. Crit Rev Oncol Hematol. 2020 Dec;156:103090. doi: 10.1016/j.critrevonc.2020.103090. Epub 2020 Aug 26.
PubMed 33091800
Wang SL, Fang H, Song YW, Wang WH, Hu C, Liu YP, Jin J, Liu XF, Yu ZH, Ren H, Li N, Lu NN, Tang Y, Tang Y, Qi SN, Sun GY, Peng R, Li S, Chen B, Yang Y, Li YX. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):352-360. doi: 10.1016/S1470-2045(18)30813-1. Epub 2019 Jan 30.
PubMed 30711522
Coles CE, Haviland JS, Kirby AM, Griffin CL, Sydenham MA, Titley JC, Bhattacharya I, Brunt AM, Chan HYC, Donovan EM, Eaton DJ, Emson M, Hopwood P, Jefford ML, Lightowlers SV, Sawyer EJ, Syndikus I, Tsang YM, Twyman NI, Yarnold JR, Bliss JM; IMPORT Trial Management Group. Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial. Lancet. 2023 Jun 24;401(10394):2124-2137. doi: 10.1016/S0140-6736(23)00619-0. Epub 2023 Jun 8.
PubMed 37302395
Haviland JS, Bentzen SM, Bliss JM, Yarnold JR; START Trial Management Group. Prolongation of overall treatment time as a cause of treatment failure in early breast cancer: An analysis of the UK START (Standardisation of Breast Radiotherapy) trials of radiotherapy fractionation. Radiother Oncol. 2016 Dec;121(3):420-423. doi: 10.1016/j.radonc.2016.08.027. Epub 2016 Sep 22.
PubMed 27666929
Lievens Y. Hypofractionated breast radiotherapy: financial and economic consequences. Breast. 2010 Jun;19(3):192-7. doi: 10.1016/j.breast.2010.03.003.
PubMed 20511069
Marta GN, Ramiah D, Kaidar-Person O, Kirby A, Coles C, Jagsi R, Hijal T, Sancho G, Zissiadis Y, Pignol JP, Ho AY, Cheng SH, Offersen BV, Meattini I, Poortmans P. The Financial Impact on Reimbursement of Moderately Hypofractionated Postoperative Radiation Therapy for Breast Cancer: An International Consortium Report. Clin Oncol (R Coll Radiol). 2021 May;33(5):322-330. doi: 10.1016/j.clon.2020.12.008. Epub 2020 Dec 23.
PubMed 33358283
FAST Trialists group; Agrawal RK, Alhasso A, Barrett-Lee PJ, Bliss JM, Bliss P, Bloomfield D, Bowen J, Brunt AM, Donovan E, Emson M, Goodman A, Harnett A, Haviland JS, Kaggwa R, Morden JP, Robinson A, Simmons S, Stewart A, Sydenham MA, Syndikus I, Tremlett J, Tsang Y, Wheatley D, Venables K, Yarnold JR. First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol. 2011 Jul;100(1):93-100. doi: 10.1016/j.radonc.2011.06.026.
PubMed 21752481
Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, Chan C, Churn M, Cleator S, Coles CE, Goodman A, Harnett A, Hopwood P, Kirby AM, Kirwan CC, Morris C, Nabi Z, Sawyer E, Somaiah N, Stones L, Syndikus I, Bliss JM, Yarnold JR; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020 May 23;395(10237):1613-1626. doi: 10.1016/S0140-6736(20)30932-6. Epub 2020 Apr 28.
PubMed 32580883
Lewis P, Brunt AM, Coles C, Griffin S, Locke I, Roques T; Breast Radiotherapy Consensus Working Group. Moving Forward Fast with FAST-Forward. Clin Oncol (R Coll Radiol). 2021 Jul;33(7):427-429. doi: 10.1016/j.clon.2021.04.007. Epub 2021 May 14. No abstract available.
PubMed 33994270

Interested in taking part?

Andrei Fodor, MD

+390226437634

fodor.andrei@hsr.it

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Five Fractions Ultrahypofractionated Whole Breast Radiotherapy and Simultaneous Integrated Boost to the Tumor Bed, for Breast Cancer Patients With Unfavorable Characteristics
ClinicalTrials.gov ID: NCT07020780
Acronym / sponsor ID: HY FIVE
Conditions: Breast Cancer
Keywords: Breast Cancer, Whole Breast Irradiation, Simultaneous Integrated Boost, Adjuvant Radiotherapy, Utrahypofractionated Radiotherapy, Moderately Hypofractionated Radiotherapy
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 458 participants (estimated)
Lead sponsor: IRCCS San RaffaeleUniversity, hospital or other
Study start: 25 Jul 2025 (actual)
Primary completion: 30 Jun 2029 (estimated)
Study completion: 30 Jun 2035 (estimated)
First posted: 13 Jun 2025 (actual)
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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: A total of 458 patients are expected to be enrolled in this prospective, randomized study. A power of 80% and a significance level α of 5% are used to calculate the sample size. The hypothesis is that the proportion of patients free from local recurrence 5 years after the end of treatment is not less than 95.4%, with a margin of 5%. A total of 218 patients per arm are needed, and an additional 5% (22 patients) to compensate for dropouts.

Arm	Type	Receives
Arm 1- Five fractions radiotherapy	Experimental	Radiation: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bedPatients in the study (randomized to arm 1) will be treated to the whole breast to a total dose (TD) of 26 Gy in 5 fractions, with simultaneous integrated boost (SIB) to a TD of 30 Gy to the tumor bed. For each patient, an IMRT (intensity modulated radiotherapy) treatment plan will be created to ensure adequate coverage of the treatment volumes and the tolerability of the Organs At Risk (OAR). Specific, already validated dose-volume constraints will be applied for the evaluation of OARs. The dose-volume histogram (DVH) for the Gross Tumor Volume (GTV), Clinical Target Volume (CTV), PTV, and OAR will be calculated in order to achieve the best optimization in terms of tolerability and efficacy.
Arm 2- Fifteen fractions radiotherapy	Active comparator	Radiation: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bedPatients randomized to arm 2 will be treated according to the standard protocol of our department, delivering adjuvant whole breast irradiation (WBI) to a total dose (TD) of 40.05 Gy in 15 fractions, with simultaneous integrated boost (SIB) to the tumor bed to a TD of 48 Gy.

Who may qualify

Ages: 18 to 70 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Histological diagnosis of breast cancer
Patients younger than 40 years regardless of histological subtype, or patients between 40 and 70 years with lobular carcinoma, histological subtypes Luminal B Her2 positive, or with hormone receptors negative and Her2 positive (ErbB2), or triple negative (TNBC)
Signed informed consent
Clinical stage T1-T3, Nx-N3
Negative surgical margins (≥ 0.2 cm)

Key exclusion criteria (13 listed)

Patients with favorable characteristics (Luminal A, Luminal B Her2 negative, ≥ 40 years) undergoing partial irradiation
Patients who have undergone mastectomy
Multicentric tumors
Positive or close surgical margins (<0.2 cm)
BRCA1/2 positive (only if known)

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
Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bedAlso: Ultrahypofractionated WBI with SIBExperimental arm (arm 1-five fractions WBI) patients will be treated to a total dose (TD) of 26 Gy in 5 fractions to whole breast, and a simultaneous integrated boost (SIB) to a TD of 30 Gy to the tumor bed, while arm 2-fifteen-fractions WBI patients with 40 Gy/15 fractions to PTV, and 48 Gy SIB to the tumor bed.	Radiation	Arm 1- Five fractions radiotherapy, Arm 2- Fifteen fractions radiotherapy

Primary outcome

Local Relapse Free Survival (LRFS)
Time frame: 5 years
o demonstrate the non-inferiority of local control (local relapse free survival - LRFS) of the study treatment (delivered in five fractions) compared to the department's standard WBI treatment (delivered in 15 fractions).

21 secondary outcomes

Acute toxicity
Time frame: 1 month
Acute toxicity
Time frame: 3 months
Late RTOG toxicity
Time frame: 5 years
Late CTCAE toxicity
Time frame: 5 years
Local Control
Time frame: 5 years
Ipsilateral Breast Tumor Recurrence (IBTR)
Time frame: 5 years
Regional Relapse-Free Survival (RRFS)
Time frame: From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years
Distant Metastasis-Free Survival (DMFS)
Time frame: From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years
Disease-Free Survival (DFS)
Time frame: From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years
Breast Cancer Specific Survival (BCSS)
Time frame: From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years
Overall Survival (OS)
Time frame: From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years
Cosmesis
Time frame: 5 years
Acute toxicity interim analysis
Time frame: 3 months
Late toxicity interim analysis
Time frame: 42 months
Local relapse interim analysis
Time frame: 42 months
Incidence of Treatment-Emergent Adverse Events as assessed with breast tumor specific quality of life questionnaires
Time frame: 5 years
Modeling of organ movement
Time frame: 15 days
Radiomics
Time frame: 5 years
Predictive factors for toxicity
Time frame: 5 years
Predictive factors for disease progression
Time frame: 5 years
Predictive factors for death
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 22 Oct 2026.
Results publication: PubMed 18355913START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008 Mar 29;371(9618):1098-107. doi: 10.1016/S0140-6736(08)60348-7. Epub 2008 Mar 19.
Results publication: PubMed 8931610Clark RM, Whelan T, Levine M, Roberts R, Willan A, McCulloch P, Lipa M, Wilkinson RH, Mahoney LJ. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group. J Natl Cancer Inst. 1996 Nov 20;88(22):1659-64. doi: 10.1093/jnci/88.22.1659.
Results publication: PubMed 20147717Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, Shelley W, Grimard L, Bowen J, Lukka H, Perera F, Fyles A, Schneider K, Gulavita S, Freeman C. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010 Feb 11;362(6):513-20. doi: 10.1056/NEJMoa0906260.
Results publication: PubMed 30379626Shaitelman SF, Lei X, Thompson A, Schlembach P, Bloom ES, Arzu IY, Buchholz D, Chronowski G, Dvorak T, Grade E, Hoffman K, Perkins G, Reed VK, Shah SJ, Stauder MC, Strom EA, Tereffe W, Woodward WA, Amaya DN, Shen Y, Hortobagyi GN, Hunt KK, Buchholz TA, Smith BD. Three-Year Outcomes With Hypofractionated Versus Conventionally Fractionated Whole-Breast Irradiation: Results of a Randomized, Noninferiority Clinical Trial. J Clin Oncol. 2018 Oct 31;36(35):JCO1800317. doi: 10.1200/JCO.18.00317. Online ahead of print.
Results publication: PubMed 35934006Chua BH, Link EK, Kunkler IH, Whelan TJ, Westenberg AH, Gruber G, Bryant G, Ahern V, Purohit K, Graham PH, Akra M, McArdle O, O'Brien P, Harvey JA, Kirkove C, Maduro JH, Campbell ID, Delaney GP, Martin JD, Vu TTT, Muanza TM, Neal A, Olivotto IA; BIG 3-07/TROG 07.01 trial investigators. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study. Lancet. 2022 Aug 6;400(10350):431-440. doi: 10.1016/S0140-6736(22)01246-6.
Results publication: PubMed 34973228Meattini I, Becherini C, Boersma L, Kaidar-Person O, Marta GN, Montero A, Offersen BV, Aznar MC, Belka C, Brunt AM, Dicuonzo S, Franco P, Krause M, MacKenzie M, Marinko T, Marrazzo L, Ratosa I, Scholten A, Senkus E, Stobart H, Poortmans P, Coles CE. European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer. Lancet Oncol. 2022 Jan;23(1):e21-e31. doi: 10.1016/S1470-2045(21)00539-8.
Results publication: PubMed 33091800Marta GN, Coles C, Kaidar-Person O, Meattini I, Hijal T, Zissiadis Y, Pignol JP, Ramiah D, Ho AY, Cheng SH, Sancho G, Offersen BV, Poortmans P. The use of moderately hypofractionated post-operative radiation therapy for breast cancer in clinical practice: A critical review. Crit Rev Oncol Hematol. 2020 Dec;156:103090. doi: 10.1016/j.critrevonc.2020.103090. Epub 2020 Aug 26.
Results publication: PubMed 30711522Wang SL, Fang H, Song YW, Wang WH, Hu C, Liu YP, Jin J, Liu XF, Yu ZH, Ren H, Li N, Lu NN, Tang Y, Tang Y, Qi SN, Sun GY, Peng R, Li S, Chen B, Yang Y, Li YX. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):352-360. doi: 10.1016/S1470-2045(18)30813-1. Epub 2019 Jan 30.
Results publication: PubMed 37302395Coles CE, Haviland JS, Kirby AM, Griffin CL, Sydenham MA, Titley JC, Bhattacharya I, Brunt AM, Chan HYC, Donovan EM, Eaton DJ, Emson M, Hopwood P, Jefford ML, Lightowlers SV, Sawyer EJ, Syndikus I, Tsang YM, Twyman NI, Yarnold JR, Bliss JM; IMPORT Trial Management Group. Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial. Lancet. 2023 Jun 24;401(10394):2124-2137. doi: 10.1016/S0140-6736(23)00619-0. Epub 2023 Jun 8.
Results publication: PubMed 27666929Haviland JS, Bentzen SM, Bliss JM, Yarnold JR; START Trial Management Group. Prolongation of overall treatment time as a cause of treatment failure in early breast cancer: An analysis of the UK START (Standardisation of Breast Radiotherapy) trials of radiotherapy fractionation. Radiother Oncol. 2016 Dec;121(3):420-423. doi: 10.1016/j.radonc.2016.08.027. Epub 2016 Sep 22.
Results publication: PubMed 20511069Lievens Y. Hypofractionated breast radiotherapy: financial and economic consequences. Breast. 2010 Jun;19(3):192-7. doi: 10.1016/j.breast.2010.03.003.
Results publication: PubMed 33358283Marta GN, Ramiah D, Kaidar-Person O, Kirby A, Coles C, Jagsi R, Hijal T, Sancho G, Zissiadis Y, Pignol JP, Ho AY, Cheng SH, Offersen BV, Meattini I, Poortmans P. The Financial Impact on Reimbursement of Moderately Hypofractionated Postoperative Radiation Therapy for Breast Cancer: An International Consortium Report. Clin Oncol (R Coll Radiol). 2021 May;33(5):322-330. doi: 10.1016/j.clon.2020.12.008. Epub 2020 Dec 23.
Individual participant dataSharing planned: Yes. The data that support the findings of this study (anonymized individual participant data) are available on request from the corresponding author to researchers who provide a methodologically sound proposal. Requests made to the corresponding author will be evaluated by the Lombardy Territorial Ethics Committee 1

Related trials for Breast Cancer

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

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.

Andrei Fodor, MD contact

+390226437634

fodor.andrei@hsr.it

Roberta Tummineri, MD contact

+390226435452

tummineri.roberta@hsr.it

Andrei Fodor, MD principal investigator

IRCCS San Raffaele Scientific Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed in people with Breast Cancer, run by IRCCS San Raffaele at 1 site in Italy.

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 9 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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?

Contact Andrei Fodor, MD (+390226437634, fodor.andrei@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Local Relapse Free Survival (LRFS) (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 NCT07020780, which also lists 45 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 22 Oct 2026.