Clinical trial NCT01247233: Standard or Hypofractionated Radiotherapy Versus Accelerated Partial Breast Irradiation (APBI) for Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Lumpectomy
Keywords: breast cancer
Accelerated Partial Breast Irradiation
invasive cancer
Hypofractionated Irradiation
Lumpectomy
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2010-11-24
Enrollment: 1006
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: rate of local recurrence
timeFrame: 5 years
Secondary outcomes:
measure: Ipsilateral breast recurrence-free survival
timeFrame: 10 years
measure: Nodal regional recurrence-free survival
timeFrame: 10 years
measure: Distant recurrence-free survival
timeFrame: 10 years
measure: Disease-specific survival
timeFrame: 10 years
measure: Overall survival
timeFrame: 10 years
measure: Toxicities: Measurement of the rate and type of toxicity (acute and late toxic effects)
timeFrame: 10 years
measure: Cosmetic: comparison of the cosmetic result (according to both the physician and the patient)
timeFrame: 10 years
measure: Quality of Life and Satisfaction
timeFrame: 10 years
measure: Medico-economic study
timeFrame: 3 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: Centre de traitement des Hautes energie - Clinique de l'Europe
city: Amiens
country: France
facility: Centre Hospitalier Universitaire
city: Bordeaux
country: France
facility: Institut Bergonié
city: Brive
country: France
facility: Centre Hospitalier
city: Caen
country: France
facility: Centre Francois Baclesse
city: Chambery
country: France
facility: CH Chambery
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Dechy
country: France
facility: Centre Leonard de Vinci
city: Grenoble
country: France
facility: CHU Michallon
city: Libourne
country: France
facility: Hôpital Robert Boulin
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montauban
country: France
facility: Clinique du Pont de Chaume
city: Montpellier
country: France
facility: CRLC Val d'Aurelle
city: Montélimar
country: France
facility: Centre Hospitalier
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Nancy
country: France
facility: Centre d'Oncologie de Gentilly
city: Neuilly sur Seine
country: France
facility: Clinique Hartmann
city: Nice
country: France
facility: Centre de Haute Energie
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpétrière
city: Paris
country: France
facility: Hopital Tenon
city: Paris
country: France
facility: Saint Louis Hospital
city: Perpignan
country: France
facility: Centre Catalan d'Oncologie
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Roanne
country: France
facility: CH de Roanne
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Priest en Jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Strasbourg
country: France
facility: Centre Paul Stauss
city: Valence
country: France
facility: Centre Marie Curie
city: Vandoeuvre les Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Henri Mondor Hospital AP-HP, Créteil, France
name: Yazid Belkacemi, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oscar Lambret Hospital, Lille, France
name: Eric Lartigau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Cancérologie de Montpellier, Montpellier, France
name: Céline Bourgier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Belkacemi Y, Bourgier C, Kramar A, Auzac G, Dumas I, Lacornerie T, Mege JP, Mijonnet S, Lemonnier J, Lartigau E. SHARE: a French multicenter phase III trial comparing accelerated partial irradiation versus standard or hypofractionated whole breast irradiation in breast cancer patients at low risk of local recurrence. Clin Adv Hematol Oncol. 2013 Feb;11(2):76-83.