Clinical trial NCT02386371: Intraoperative Radiotherapy After Local Recurrence in Breast Cancer
Official title: Feasibility Clinical Trial of Intraoperative Radiotherapy (IORT) and Second Breast-conserving-surgery After Local Recurrence of Breast Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Carcinoma
Lead sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Sponsor class: OTHER
First posted: 2015-03-11
Enrollment: 66
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators propose a prospective, multicenter, single arm Phase II design to evaluate the feasibility of repeated breast-conserving surgery combined with re- irradiation using IORT after local recurrence of breast carcinoma.

Detailed description: Currently, the rate of ipsilateral breast tumor recurrence (IBTR) after breast- conserving surgery and radiotherapy remains at 10% at 10 years to 15% at 20 years, respectively. IBTR is an independent predictor of poor survival with a 3 to 4.6 increased risk of cancer-related death.

In a heterogeneous population, local control remains a major therapeutic challenge for these relapses, especially those considered of better prognosis, namely occurring late and of low histological grade. Therapeutic de-escalation is possible for these relapses to avoid a mutilating and often traumatic mastectomy.

However, this second conservative surgery has a high rate of second local relapse (19 to 50% at 5 years) due to the absence of a re-irradiation, rendered impossible by the problem of tolerance of previously irradiated tissues.

Retrospective or prospective studies on partial breast irradiation (PBI) in adjuvant setting report promising results, both in terms of tolerance (saving healthy tissue) and local control (74% to 100% at 5 years). Used techniques include brachytherapy, external beam radiotherapy and intraoperative radiotherapy (IORT).

IORT is now the subject of renewed interest in breast cancer. It has the advantages of high-precision ballistics on the operated area and of preservation of healthy tissue. To date, no prospective data, however, have been published in the indication of ipsilateral breast recurrence.

A prospective, multicenter, single arm Phase II design will evaluate the feasibility of repeated breast-conserving surgery combined with re- irradiation using IORT after local recurrence of breast carcinoma.

Eligibility criteria: Inclusion Criteria:

* Histologically proven non-lobular invasive breast recurrence
* Time from whole breast radiation following the initial lumpectomy \>5 years
* Unifocal tumor
* Recurrent tumor size ≤ 2 cm
* Adequate breast size for a second breast-conserving surgery with acceptable cosmetic result
* Bilateral breast mammogram within 90 days prior to study entry
* Breast MRI within 90 days prior to study entry
* Histological grade I-II
* Estrogen-receptor-positive tumor (ER+)
* Cerb2-negative tumor
* N0
* M0
* Prior radiotherapy delivered within a standard fractionation schedule
* Performance status (ECOG) 0-1
* Women ≥ 50 years -Absence of any psychological, familial, sociological, or geographical conditions with a potential to hamper compliance with the study and follow- up schedule
* Affiliated to the French Health Insurance regimen
* Written and signed informed consent form.

Exclusion Criteria:

* Multifocal and/or multicenter recurrence
* Lobular carcinoma
* Estrogen-receptor-negative tumor (ER-)
* Cerb2 (her2) overexpressed - breast cancer
* Extensive intraductal component (EIC) on biopsy
* Lymph vessel invasion on biopsy
* N1-3 status: Regional cytological or histologically proven node recurrence
* M1 status: Metastatic disease
* cT4 (Skin or muscle involvement) or Paget's disease of the nipple
* Prior radiotherapy delivered within an accelerated or hypo-fraction schedule
* Prior malignancy other than non-melanoma skin cancer unless the patient has been disease free for at least 5 years
* Patients with a small breast volume, technically unsatisfactory for a second conservative surgery or intraoperative breast irradiation.
* Preoperative chemotherapy or hormone therapy for local relapse
* Connective tissue disease or scleroderma, contraindicating radiotherapy
* Known BRCA1/2 gene mutation (genetic testing is not required)

Primary outcomes:
measure: The Tolerance of RIOP (Intra Operative Radiotherapy) in Patients With Delayed Local Recurrences, After a Second Conservative Treatment of Breast Cancer
timeFrame: Up to 12 months post radiation
Secondary outcomes:
measure: Rate of Early and Late Toxicities
timeFrame: from the baseline to 5 years after treatment
measure: Local Relapse-free Survival
timeFrame: from the baseline to 5 years after treatment
measure: Metastasis Relapse-free Survival
timeFrame: from the baseline to 5 years after treatment
measure: Disease-free Survival.
timeFrame: from the baseline to 5 years after treatment
measure: Overall Survival
timeFrame: from the baseline to 5 years after treatment
measure: Free Interval Without Mastectomy.
timeFrame: from the baseline to 5 years after treatment
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Brest
country: France
facility: Chu Brest
city: Dijon
country: France
facility: Centre George Francois Leclerc
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: CHU La TIMONE
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Montpellier
country: France
facility: ICM
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest
Study officials:
affiliation: Institut régional du Cancer - Val d'Aurelle
name: LEMANSKI Claire
role: STUDY_CHAIR
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