No Axillary sUrgical Treatment In Clinically Lymph Node Negative Patients After UltraSonography

NCT ID: NCT04303715

Last Updated: 2023-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

1734 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-15

Study Completion Date

2027-12-31

Brief Summary

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NAUTILUS study is a prospective, multicenter, RCT. Clinically T1,T2, node negative BCS candidates with no evidence of metastases in AUS are 1:1 randomized into no SLNB group and SLNB group.

NAUTILUS study aim to establish the minimally invasive treatment of breast cancer by reexamining the necessity of sentinel lymph node biopsy among patients with invasive breast cancer who have tumors under 5cm, are clinically node-negative, and are having breast conserving surgery performed.

Detailed Description

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\[Background\] Skipping ALND, the follow-up treatment in SN-positive patients, has non-inferior oncological outcomes compared to SLNB-only group, given that there is no severe SN metastases.

Axillary ultrasound can effectively exclude high nodal burden, showing 95% NPV in a systematic review.

SLNB has morbidity including lymphedema, limited range of motion, pain, and other post-surgical complications, eventually leading to reduced quality of life.

Considering improvement of imaging modalities and adjuvant care, survival outcome of SLNB must be re-evaluated. Especially research reflective of the regional specificities of Korea and Asia-Pacific is needed.

\[Study design\] Prospective, Multicenter, RCT.

\[Statistical considerations\] According to Z0011 trial, 5yr DFS in eligible patients is expected to be 86%, which is between previous data of 88.6% in cT1,2 and SN-negative patients4, and 83.9% in cT1,2 and 1-2 SN-positive patients.

Non-inferiority margin is set at 5%. With 5% significance level and 80% power, 780 patients are needed in each group. Assuming a 10% drop out rate, 1734 patients need to be recruited.

\[Screening and Randomization\] Participants undergo screening tests that assess eligibility according to inclusion/exclusion criteria.

In order to identify axillary lymph node metastases, axillary ultrasound is first performed by radiologists. Patients showing normal features are enrolled, while for conditionally normal patients, with only 1 suspicion of low nodal burden, axillary lymph node biopsy should be performed. Suspicious patients are excluded under following conditions: patients with 1 or more suspicion of high nodal burden, 2 or more suspicion of low nodal burden, or T2 invasive lobular carcinoma patients with 1 or more low nodal burden. The severity of nodal burden is defined through the criteria.

Patients who underwent radiological axillary staging are randomly assigned (1:1) to the study arm and the control arm before surgical care. Stratification is done based on trial centers and tumor sizes.

\[Post-surgical care\] All patients are planned to receive ipsilateral whole breast radiation. Patients randomized to non-SLNB arm are recommended to follow high tangential radiotherapy protocol, in which upper margin of radiation field includes axillary level I and II or lies within 2CM from humeral head.

Additional treatment may be performed if deemed necessary by the researcher

\[Objectives\]

1. Primary objective

\- 5yr invasive Disease Free Survival
2. Secondary objectives

* 5yr Overall Survival
* 5yr Distant Metastasis Free Survival
* Axillary recurrence rate
* Patient reported AE
* QoL

Conditions

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Breast Cancer Sentinel Lymph Node

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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No SLNB group

The study arm - BCS without SLNB

Group Type EXPERIMENTAL

No SLNB

Intervention Type PROCEDURE

BCS only. Ommission of SLNB by axilla ultrasonography among selective breast cancer patients

SLNB group

The Control Arm - BCS with SLNB(+/-ALND)

Group Type OTHER

SLNB

Intervention Type PROCEDURE

BCS with SLNB(+/-ALND)

Interventions

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No SLNB

BCS only. Ommission of SLNB by axilla ultrasonography among selective breast cancer patients

Intervention Type PROCEDURE

SLNB

BCS with SLNB(+/-ALND)

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Women ≥ 19 years
* Invasive unilateral breast carcinoma with histological confirmation
* History of invasive breast cancer
* Histologically or radiologically no suspicion of distant metastases
* Performance status corresponding to ECOG grade 0-2
* Tumor size clinically and radiologically ≤ 5cm, independent of hormone receptor and HER2 status
* Clinically and sonographically negative axillary lymph nodes before biopsy; core needle biopsy or fine needle aspiration of suspicious lymph node required
* BCS candidate with postoperative whole-breast irradiation and adequate systemic therapy
* No psychological and geographical restriction in follow-up
* Written informed consent

Exclusion Criteria

* History of any cancer in the previous 5 years
* Bilateral breast cancer
* Invasive breast cancer treated with neoadjuvant therapy
* Tumor size clinically and radiologically \> 5cm
* Mastectomy candidate
* Pregnancy and breastfeeding
* Male breast cancer
* Unable to understand and fill out questionnaires
Minimum Eligible Age

19 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Evidence-Based Healthcare Collaborating Agency

OTHER_GOV

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wonshik Han

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

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Seoul National University Hospital

Seoul, , South Korea

Site Status

Countries

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South Korea

References

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Jung JG, Ahn SH, Lee S, Kim EK, Ryu JM, Park S, Lim W, Jung YS, Chung IY, Jeong J, Chang JH, Shin KH, Chang JM, Moon WK, Han W. No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial. BMC Cancer. 2022 Feb 20;22(1):189. doi: 10.1186/s12885-022-09273-1.

Reference Type DERIVED
PMID: 35184724 (View on PubMed)

Chang JM, Shin HJ, Choi JS, Shin SU, Choi BH, Kim MJ, Yoon JH, Chung J, Kim TH, Han BK, Kim HH, Moon WK. Imaging Protocol and Criteria for Evaluation of Axillary Lymph Nodes in the NAUTILUS Trial. J Breast Cancer. 2021 Dec;24(6):554-560. doi: 10.4048/jbc.2021.24.e47. Epub 2021 Nov 24.

Reference Type DERIVED
PMID: 34877830 (View on PubMed)

Other Identifiers

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NAUTILUS study

Identifier Type: -

Identifier Source: org_study_id