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

Official title

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

Overview

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 SIB to the tumor bed to a total dose of 48 Gy (standard treatment), for young or unfavorable breast cancer patients.

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.

Interventions

• Radiation Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed
  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.

Primary outcome measures

• Local Relapse Free Survival (LRFS) [Time frame: 5 years]

Secondary outcome measures (12)

• Acute toxicity [Time frame: 1 month]
• Acute toxicity [Time frame: 3 months]
• Late toxicity [Time frame: 5 years]
• Late 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]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• 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
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 1 center

• IRCCS San Raffaele Scientific Institute — Milan

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 brea PMID 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. PMID 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. PMID 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, Noninferi PMID 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 PMID 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 do PMID 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. PMID 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( PMID 30711522

Identifiers

NCT: NCT07020780 · HY FIVE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗