Standard or Hypofractionated Radiotherapy Versus Accelerated Partial Breast Irradiation (APBI) for Breast Cancer

Breast Cancer Clinical Trial

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Official title:

Phase III Multicentric Trial Comparing Accelerated Partial Breast Irradiation (APBI) Versus Standard or Hypofractionated Whole Breast Irradiation in Low Risk of Local Recurrence of Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01247233
• Other study ID #: RTS02-SHARE
• Secondary ID: 2010-A00243-36UC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 27, 2010
• Est. completion date: October 2025

Study information

• Verified date: April 2024
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The standard treatment for localized breast cancer is based on conservative surgery (when possible) followed by radiation therapy (RT) delivered to the whole breast. The recommended total RT dose is 45 to 50 Gy delivered in 4.5 to 5 weeks followed by a 10 to 16 Gy boost to the tumor bed for 1 to 1.5 weeks. The rationale for the development of APBI was based on the difficulty for many patients to reach RT centers to receive standard whole breast irradiation (WBI) after conservative surgery. APBI offers decreased overall treatment time and several theoretical advantages over WBI, including a decrease in dose delivered to uninvolved portions of the breast and adjacent organs. If equivalence between the two treatments can be shown, then APBI will be considered as a historic evolution in breast cancer management. In this phase III trial, designed in postmenopausal women >50 years of age, the objective is to compare the effectiveness and safety of APBI compared with whole breast irradiation. This study is also designed to ensure high quality criteria for surgery, pathology and RT techniques in the 3 arms and will allow to provide data on economics and costs.

Description:

Following breast conservative surgery, patients will be stratified according to the following prognostic factors using a minimisation technique: age (<70 vs ≥70), HER2 status (HER2+ vs HER2-), hormonal receptor status (RH+ vs RH-) and lymph node invasion (pN0 vs pN0i+). Patients will be allocated to receive either standard treatment, hypofractionated treatment or APBI. Radiation therapy should be started between 4 and 12 weeks after the last surgery. Patients treated with standard whole breast irradiation will receive a total dose of 50 Gy in 25 fractions, 2 Gy per day, 5 days a week. The boost of 16 Gy will be delivered in 8 fractions for all patients after completion of the 50 Gy, without interruption. All patients will receive one fraction per day, 5 fractions a week. Patients treated with hypofractionated irradiation will receive a total dose of either 40 Gy (in 15 fractions, 2.66 Gy per day) or 42.5 Gy (in 16 fractions, 2.65 Gy per day) 5 days a week. Patients treated with APBI will receive a total dose of 40 Gy in 10 fractions, delivered twice a day over a time period of 5-7 days. Each daily dose must be separated by 6 hours. Patients will be followed at 3 and 6 month after the last dose of irradiation, at 12 months after the date of last surgery and then on a yearly basis during 10 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1006
• Est. completion date: October 2025
• Est. primary completion date: December 7, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Women aged =50 years
• Menopausal status confirmed
• Pathology confirmation of invasive carcinoma (all types)
• Complete tumor removal and conservative surgery
• Pathologic tumor size of invasive carcinoma =2 cm (including the in situ component) pT1
• All histopathologic grades
• Clear lateral margins for the invasive and in situ disease (>2 mm)
• pN0 or pN(i+)
• No metastasis
• Radiotherapy should be started more than 4 weeks and less than 12 weeks after last surgery
• Surgical clips (4 to 5 clips in the tumor bed)
• No prior breast or mediastinal radiotherapy
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Information to the patient and signed informed consent

Exclusion Criteria:

• Multifocal invasive ductal carcinoma defined as the presence of at least two distinct tumors that are separated by normal tissue or when the distance between the two lesions does not permit conservative surgery
• Bilateral breast cancer
• No or less than 4 surgical clips in the tumor bed
• Nodal involvement : pN1 (including micrometastasis, mi+), pN2, pN3
• Metastatic disease
• internal mammary node involvement or supraclavicular lymph node involvement
• Indication of chemotherapy or trastuzumab
• Involved or close lateral margins for the invasive and /or in situ components (<2 mm) AND impossibility to re-operate or impossible to perform another conservative surgery
• Patients with known BRCA1 or BRCA2 mutations
• Previous mammoplasty
• Previous homolateral breast and/or mediastinal irradiation
• Previous invasive cancer (except basocellular epithelioma or in situ carcinoma of the cervix)
• No geographical, social or psychologic reasons that would prevent study follow

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Lumpectomy

Intervention

Radiation:
• Whole Breast Irradiation + Boost or Hypofractionated irradiation
Whole Breast Irradiation 50 Gy + Boost 16 Gy or Whole breast, either 40 Gy in 15 fractions in 3 weeks or 42.5 Gy in 16 fractions in 3 weeks
• Accelerated partial breast irradiation
Tumor bed 40 Gy in 10 fractions, 2 fractions of 4 Gy per day in 5 to 7 days.

Locations

Country	Name	City	State
France	Centre de traitement des Hautes energie - Clinique de l'Europe	Amiens
France	Centre Hospitalier Universitaire	Amiens
France	Institut Bergonié	Bordeaux
France	Centre Hospitalier	Brive
France	Centre Francois Baclesse	Caen
France	CH Chambery	Chambery
France	Hopital Henri Mondor	Creteil
France	Centre Leonard de Vinci	Dechy
France	CHU Michallon	Grenoble
France	Hôpital Robert Boulin	Libourne
France	Centre Oscar Lambret	Lille
France	CHU Dupuytren	Limoges
France	Centre Léon Bérard	Lyon
France	Institut Paoli Calmettes	Marseille
France	Clinique du Pont de Chaume	Montauban
France	Centre Hospitalier	Montélimar
France	CRLC Val d'Aurelle	Montpellier
France	Centre Hospitalier de Mulhouse	Mulhouse
France	Centre d'Oncologie de Gentilly	Nancy
France	Clinique Hartmann	Neuilly sur Seine
France	Centre de Haute Energie	Nice
France	Groupe Hospitalier Pitié Salpétrière	Paris
France	Hopital Tenon	Paris
France	Saint Louis Hospital	Paris
France	Centre Catalan d'Oncologie	Perpignan
France	Institut Jean Godinot	Reims
France	Centre Eugène Marquis	Rennes
France	CH de Roanne	Roanne
France	Centre Henri Becquerel	Rouen
France	Institut de Cancérologie de la Loire	Saint Priest en Jarez
France	Centre Paul Stauss	Strasbourg
France	Centre Marie Curie	Valence
France	Centre Alexis Vautrin	Vandoeuvre les Nancy
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rate of local recurrence	To estimate and compare the rate of local recurrence between the experimental and control arms.	5 years
Secondary	Ipsilateral breast recurrence-free survival	To evaluate Ipsilateral breast recurrence-free survival	10 years
Secondary	Nodal regional recurrence-free survival	To evaluate nodal regional recurrence-free survival	10 years
Secondary	Distant recurrence-free survival	To evaluate distant recurrence-free survival	10 years
Secondary	Disease-specific survival	To evaluate disease-specific survival	10 years
Secondary	Overall survival	To evaluate the overall survival	10 years
Secondary	Toxicities: Measurement of the rate and type of toxicity (acute and late toxic effects)	To evaluate rates and type of acute and late toxicities	10 years
Secondary	Cosmetic: comparison of the cosmetic result (according to both the physician and the patient)	To evaluate Cosmetic results (Patient and Physician evaluations)	10 years
Secondary	Quality of Life and Satisfaction	To evaluate the patient quality of life and patient satisfaction	10 years
Secondary	Medico-economic study	To evaluate the cost of APBI compared with Standard and Hypofractionated irradiation	3 years