Sentinel Node Vs Observation After Axillary Ultra-souND (SOUND)

• ClinicalTrials.gov Identifier: NCT02167490
• Recruitment Status: Active, not recruiting
• First Posted: June 19, 2014
• Last Update Posted: February 17, 2023
• Sponsor: European Institute of Oncology
• Information provided by (Responsible Party): European Institute of Oncology

Study Description

Brief Summary:

The hypothesis of this trial are that:

• avoiding axillary surgery does not worsen the outcome of patients with small breast cancer the absence of the pathological information on the risk of recurrence given by nodal status is not worsening outcome of these patients
• pre-operative imaging of the axilla can identify patients with clinically relevant nodal burden.

The aims of this prospective randomized study are:

• to verify whether, in presence of a negative preoperative axillary assessment, SLN can be spared
• to verify whether, in presence of a negative preoperative axillary assessment, the decision on adjuvant medical treatment can be taken according only to the biology of the tumour without the prognostic information achieved by SLNB on the nodal status
• to verify whether, in presence of a negative preoperative axillary assessment, the patients' quality of life can be improved by a less invasive surgical procedure.

Condition or disease	Intervention/treatment	Phase
Early Stage Breast Carcinoma	Procedure: Arm 1: sentinel node biopsy	Not Applicable

Detailed Description:

Sentinel lymph node biopsy (SLNB) is the standard approach for axillary staging in patients with breast cancer worldwide. The evident trend of breast cancer treatment is going towards minimizing axillary surgery, even in presence of involvement of the sentinel lymph node (SLN). In fact, it is well known that removal of lymph nodes is performed with staging purposes and to improve regional control but not with curative intent. Recent data from a prospective randomized trial which compared axillary dissection vs. no further axillary surgery in presence of positive SLN did not show any difference in term of overall and disease-free survival. Moreover, to date the impact of the prognostic information of axillary lymph node status in the decision-making process is less important than in the past as the adjuvant treatment is more and more tailored on the biological features of the disease rather than on the risk of recurrence.

This is a prospective randomized controlled trial in which patients with small breast cancer (T<2 cm), with a negative preoperative assessment of the axilla (ultra-sound with FNAC in presence of doubtful findings) will be randomized into two treatment arms:

• SLNB ± axillary dissection
• No axillary surgical staging In the arm 1, no axillary dissection will be performed in case of either negative SLN or in presence of isolated tumour cells or micrometastases. SLNB will be completed by axillary dissection in presence of macrometastases diagnosed in the SLN.

The aims of this prospective randomized study are:

to verify whether, in presence of a negative preoperative axillary assessment, SLN can be spared to verify whether, in presence of a negative preoperative axillary assessment, the decision on adjuvant medical treatment can be taken according only to the biology of the tumour without the prognostic information achieved by SLNB on the nodal status to verify whether, in presence of a negative preoperative axillary assessment, the patients' quality of life can be improved by a less invasive surgical procedure.

Endpoints

The primary endpoint of the study is distant-disease free survival. This endpoint, a proxi of overall survival, will allow to have reliable results in a shorter period of time compared to overall survival.

Secondary endpoints will be the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, the disease free survival (DFS) and the overall survival (OS). Other secondary endpoints are quality of life and evaluation of type of adjuvant treatment administered.

Sample size calculation and statistical considerations

We will consider women who will undergo SLNB as the reference group, and we will test for non-inferiority the group of women not undergoing any treatment in the axilla. For the purpose of sample size calculation, the 5-year DDFS in the reference group is assumed to be 96.5%. Overall, 1560 women (780 per arm) will be enrolled to decide whether the group without treatment of the axilla is no worse than the reference group, given a margin delta of non-inferiority of 2.5% (maximum tolerable 5-years DDFS = 94%). Statistical power and one-sided type I error are set to 80% and 5%, respectively. After 3 years from the start of accrual an interim safety analysis will be performed.

Standard survival analyses and survival analyses with competing events will be performed. Multivariable Cox regression models will be applied to adjust the risk estimates of interest for other variables. The Chi-square test for trend, Chi-square test and the Fisher exact test will be used to evaluate differences in percentages between the two treatment groups, as appropriate. The T-tests will be used to evaluate differences in means for continuous variables.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1560 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Trial Comparing Sentinel Lymph Node Biopsy Vs no Axillary Surgical Staging in Patients With Small Breast Cancer and a Negative Preoperative Axillary Assessment (IEO S637/311)
• Actual Study Start Date: January 2012
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1: sentinel node biopsy; Sentinel node biopsy policy	Procedure: Arm 1: sentinel node biopsy; Sentinel node biopsy policy
No Intervention: Arm 2: observation; No axillary staging

Outcome Measures

Primary Outcome Measures :

1. Distant-disease free survival [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. Cumulative incidence of distant recurrences [ Time Frame: 6 months ]
2. Cumulative incidence of axillary recurrences [ Time Frame: 6 months ]
3. Disease free survival (DFS) [ Time Frame: 6 months ]
4. Overall survival [ Time Frame: 6 months ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• breast cancer <2 cm, and a clinically negative axilla
• any age
• candidates to receive breast conserving surgery + radiotherapy
• negative preoperative assessment of the axilla (ultra-sound with or without FNAC in case one doubtful node is found)
• written informed consent must be signed and dated by the patient and the investigator prior to inclusion.
• patients must be accessible for follow-up.

Exclusion Criteria:

• synchronous distant metastases
• previous malignancy
• bilateral breast cancer
• multicentric or multifocal breast cancer
• previous primary systemic therapy
• pregnancy or breastfeeding
• pre-operative diagnosis (cytology or histology) of axillary lymph node metastases
• pre-operative radiological evidence of multiple involved or suspicious nodes
• patients with psychiatric, addictive, or any disorder, which compromises ability to give informed consent for participation in this study.

Contacts and Locations

Locations

Chile

Instituto Oncologico Fundacion Arturo Lopez Perez

Santiago, Chile

Italy

Comprensorio Sanitario

Bolzano, Italy, 39100

Azienda Ospedaliera Spedali Civili

Brescia, Italy, 25123

Ospedale Oncologico Regionale

Cagliari, Italy, 09121

Humanitas Mater Domini

Castellanza, Italy

Ospedale S. Anna

Como, Italy, 22100

Azienda Ospedaliera Carlo Poma

Mantova, Italy, 46100

Fondazione IRCCS Istituto Nazionale Tumori

Milano, Italy, 20133

European Institute of Oncology

Milan, Italy, 20141

AOU Federico II

Napoli, Italy, 80131

Istituto Nazionale Tumori

Napoli, Italy, 80131

Ospedale San Matteo

Pavia, Italy

Ospedale Guglielmo di Saliceto

Piacenza, Italy, 29100

Ospedale Fatebenefratelli

Roma, Italy, 00186

Humanitas Cancer Center

Rozzano, Italy, 20089

Ospedale S. Anna

Torino, Italy, 10100

Spain

Health Research Institute Hospital La Fe

Valencia, Spain

Switzerland

Universitätsspital Bern Klinik und Poliklinik für Medizinische Onkologie

Bern, Switzerland

Sponsors and Collaborators

European Institute of Oncology

Investigators

• Principal Investigator: Oreste D Gentilini, MD; European Institute of Oncology

More Information

Publications:

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• Responsible Party: European Institute of Oncology
• ClinicalTrials.gov Identifier: NCT02167490
• Other Study ID Numbers: IEO S637/311
• First Posted: June 19, 2014
• Last Update Posted: February 17, 2023
• Last Verified: February 2023

Keywords provided by European Institute of Oncology:

BC; conservative surgery; SNB; AD; axillary US imaging

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases