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Single-fraction APBI for Early-stage Breast Cancer With Favorable Histological Subtypes (Breast-1F)

Not Applicable
Not yet recruiting
Conditions
Breast Cancer
Registration Number
NCT06946238
Lead Sponsor
IRCCS San Raffaele
Brief Summary

This is a prospective, randomized, monocentric, non-inferiority interventional clinical study comparing an Accelerated Partial Breast Irradiation (APBI) for the surgical bed of early-stage breast cancer patients with favorable histological subtypes, using stereotactic radiotherapy in a single dose of 15.5 Gy with Simultaneous Integrated Boost (SIB) to 21 Gy (study treatment, delivered in a single fraction) versus multifractionated radiotherapy of 30 Gy in 5 fractions (standard treatment, delivered in 5 fractions).

Detailed Description

The project refers to a study on patients with early-stage breast cancer with pathological Tumor stage (pT) from in situ (pTis) to pT2 up to 3 cm in diameter, and pathological/clinical nodal stage p/cN0, and favorable histology (Luminal A and Luminal B human epidermal growth factor receptor 2 (HER2)-negative subtypes), comparing an APBI treatment delivered with stereotactic radiotherapy to the Planning Target Volume (PTV) of the tumor bed of the breast with a total dose (TD) of 15.5 Gy in one fraction, with simultaneous integrated boost (SIB) to a TD of 21 Gy to the Gross Tumor Volume (GTV) represented by tumor bed, versus 30 Gy in 5 consecutive fractions to the PTV of the tumor bed, according to the standard APBI protocol of the department (Florence protocol).

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
311
Inclusion Criteria
  1. Histological diagnosis of breast cancer
  2. Patients aged ≥40 years
  3. Signed informed consent
  4. Stage pTis-T2, up to 3 cm in the greatest diameter
  5. Luminal A and Luminal B HER2-negative histological subtypes
  6. Negative surgical margins (≥ 0.2 cm)
  7. Negative lymph nodes at sentinel lymph node biopsy, or alternatively with imaging tests (Positron Emission Tomography (PET)/Computed Tomography (CT) and/or axillary ultrasound, and/or breast Magnetic Resonance Imaging (MRI) with and without contrast), or, in rare cases, where still performed, with axillary dissection
  8. Clinical M0 (PET/CT and/or bone scintigraphy and/or abdomen-pelvis CT with and without contrast in suspected patients), within the previous 3 months.
  9. Performance Status (PS) Eastern Cooperative Oncology Group (ECOG) ≤2
  10. No prior thoracic radiotherapy
  11. Fertile women using contraception methods initiated during oncological treatment.
Exclusion Criteria
  1. Patients aged < 40 years
  2. Tumors > 3 cm
  3. Multicentric tumors
  4. Positive or close surgical margins (<0.2 cm)
  5. Lobular carcinoma
  6. Negative hormone receptors
  7. HER2-positive
  8. BReast CAncer (BRCA) genes BRCA1 and/or BRCA2 positive (only if known)
  9. Severe systemic diseases
  10. Psychiatric or other disorders that may prevent the patient from signing informed consent
  11. Previous invasive cancer, except for skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the oral cavity or bladder)
  12. Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome)
  13. Lymph node disease (N1)
  14. Evidence of distant metastasis (M1)
  15. Contraindication to systemic treatment
  16. Pregnant women
  17. Non-compliance with the dose limits established in the treatment plan

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Ipsilateral Breast Tumor Recurrence (IBTR)5 years

To demonstrate the non-inferiority of local control (ipsilateral breast tumor recurrence - IBTR) of the study treatment (delivered in a single-fraction APBI) compared to the department's standard APBI treatment (delivered in 5 fractions).

Secondary Outcome Measures
NameTimeMethod
Acute toxicity3 months

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

Late toxicity5 years

Late toxicity evaluated with RTOG/EORTC and Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale, with 5 grades, from 0 = no change, to 5 = death for toxicity

Disease-Free Survival (DFS)From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years

Time to first any relapse: local, regional or distant

Local Control5 years

Local control of the treated site expressed in terms of local recurrence rate

Local Relapse-Free Survival (LRFS)From the date of radiotherapy end until the date of local relapse, assessed up to 5 years

Time to local recurrence

Regional Relapse-Free Survival (RRFS)From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years

Time to regional (nodal) recurrence

Distant Metastasis-Free Survival (DMFS)From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years

Time to distant (metastatic) relapse

Breast Cancer Specific Survival (BCSS)From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years

Time until death from breast cancer

Overall Survival (OS)From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years

Time until death from any cause

Cosmesis5 years

Cosmetic results evaluated with Harvard scale. It assesses the global esthetic appearance of the breast, categorized as Excellent, Good, Fair, or Poor

Acute toxicity interim analysis3 months

An interim analysis of acute toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 120 patients

Late toxicity interim analysis42 months

An interim analysis of late toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 120 patients

Local relapse interim analysis42 months

An interim analysis of local relapse rate will be performed for the first 120 patients

Trial Locations

Locations (1)

IRCCS San Raffaele Scientific Institute

🇮🇹

Milan, Italy

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