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

February 16, 2023 updated by: European Institute of Oncology

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)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

1560

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Chile
      • Santiago, Chile
        • Instituto Oncológico Fundación Arturo López Pérez
  • Italy
      • Bolzano, Italy, 39100
        • Comprensorio Sanitario
      • Brescia, Italy, 25123
        • Azienda Ospedaliera Spedali Civili
      • Cagliari, Italy, 09121
        • Ospedale Oncologico Regionale
      • Castellanza, Italy
        • Humanitas Mater Domini
      • Como, Italy, 22100
        • Ospedale S. Anna
      • Mantova, Italy, 46100
        • Azienda Ospedaliera Carlo Poma
      • Milan, Italy, 20141
        • European Institute of Oncology
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale Tumori
      • Napoli, Italy, 80131
        • AOU Federico II
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori
      • Pavia, Italy
        • Ospedale San Matteo
      • Piacenza, Italy, 29100
        • Ospedale Guglielmo di Saliceto
      • Roma, Italy, 00186
        • Ospedale Fatebenefratelli
      • Rozzano, Italy, 20089
        • Humanitas Cancer Center
      • Torino, Italy, 10100
        • Ospedale S. Anna
  • Spain
      • Valencia, Spain
        • Health Research Institute Hospital La Fe
  • Switzerland
      • Bern, Switzerland
        • Universitätsspital Bern Klinik und Poliklinik für Medizinische Onkologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Distant-disease free survival
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 6 months
6 months
Cumulative incidence of distant recurrences
Time Frame: 6 months
6 months
Cumulative incidence of axillary recurrences
Time Frame: 6 months
6 months
Disease free survival (DFS)
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Institute of Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2012

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

April 18, 2014

First Submitted That Met QC Criteria

June 18, 2014

First Posted (Estimate)

June 19, 2014

Study Record Updates

Last Update Posted (Actual)

February 17, 2023

Last Update Submitted That Met QC Criteria

February 16, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IEO S637/311

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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