Breast CancerPhase 3Neo-NAUTILUSNCT06704945
No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy
A Phase 3 study testing No axillary surgery and Axillary surgery in people with Breast Cancer and Neoadjuvant Therapy, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
NEO-NAUTILUS is a prospective, multicenter, randomized phase III clinical trial to evaluate whether omitting axillary lymph node surgery (ALND or SLNB) in clinically lymph node-negative breast cancer patients after neoadjuvant chemotherapy is non-inferior to performing SLNB in terms of 5-year disease-free survival. Read more about this study
- Who is it for?
- Ages 19 years and older, women only
- Conditions the study is for
- Breast Cancer, Neoadjuvant Therapy, Sentinel Lymph Node Biopsy
- What is being tested?
- No axillary surgery and Axillary surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 464 participants
- Where
- 1 siteSouth Korea
- Study dates
- 4 Jun 2025to 31 Dec 2034
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women aged ≥19 years.
- Histologically confirmed invasive breast carcinoma treated with neoadjuvant chemotherapy.
- Clinical staging prior to NAC: cT1-3, cN0, M0 (AJCC 8th Edition).
- If pre-NAC staging is cT1-3, cN1, M0, must meet the following criteria:
- HER2-positive or triple-negative breast cancer (TNBC).
- At least 30% reduction in tumor size on MRI after NAC (comparing pre- and post-NAC MRI).
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- Negative axillary lymph node status on ultrasound after NAC.
- Planned for breast-conserving surgery with completed neoadjuvant chemotherapy (at least half the planned regimen must be completed).
- ECOG performance status of 0-2.
- Signed written informed consent before enrollment.
Who cannot join
- History of any cancer within the past 5 years.
- Bilateral breast cancer.
- Patients requiring mastectomy.
- Tumor size >5 cm after NAC.
- Male breast cancer.
- Pregnant or breastfeeding women.
- Inability to understand and complete questionnaires.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Seoul National University Hopsital
Seoul, 03080
About this study
Official title: No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy: A Prospective, Phase III Clinical Trial
NEO-NAUTILUS is a prospective, multicenter, randomized phase III clinical trial to evaluate whether omitting axillary lymph node surgery (ALND or SLNB) in clinically lymph node-negative breast cancer patients after neoadjuvant chemotherapy is non-inferior to performing SLNB in terms of 5-year disease-free survival.
Read the detailed description
Background:
- No prospective studies have proven that axillary lymph node surgery improves survival in breast cancer patients.
- The ACOSOG Z0011 trial showed that additional axillary dissection did not improve recurrence or survival, even with a 23.7% incidence of non-sentinel node metastases.
- NSABP B-32 established the oncologic safety of SLNB, significantly reducing complications like lymphedema compared to axillary dissection. However, SLNB still carries risks of lymphedema, sensory changes, seromas, and infections.
- The trend has now shifted toward identifying candidates for omitting axillary surgery to minimize unnecessary complications.
- The SOUND trial demonstrated non-inferiority of omitting SLNB in early-stage breast cancer patients with negative axillary ultrasound. Five-year distant metastasis-free survival was comparable between SLNB and no-SLNB groups (97.7% vs. 98.0%).
- Improved ultrasound accuracy (e.g., FNR: 13.7% in SOUND; 11.3% in NAUTILUS) and the therapeutic contribution of whole-breast radiation likely support these findings.
- Patients with a complete pathological response (pCR) in the breast post-NAC rarely have residual lymph node metastases, reducing the need for axillary surgery.
- Single-arm studies (e.g., EUBREAST-01, ASICS, ASLAN) have explored omitting axillary surgery in patients with confirmed breast pCR. However, these studies face limitations due to small sample sizes, single-arm design, and the necessity of axillary surgery if pCR is not achieved.
- To address these limitations, the NEO-NAUTILUS trial proposes the first randomized trial to compare disease-free survival and local recurrence rates between patients who omit SLNB (experimental group) and those who undergo SLNB (control group) after NAC, focusing on patients deemed axillary node-negative by ultrasound.
- Being tested
- No axillary surgery, Axillary surgery
- Keywords
- Omission of axillary surgery after neoadjuvant chemotherapy, Breast cancer, Neoadjuvant chemotherapy, De-escalation, Omission of surgery
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No axillary surgeryProcedure or surgery
BCS only. Ommission of axillary surgery. No axillary surgery after neoadjuvant chemotherapy.
Axillary surgeryProcedure or surgery
BCS with SLNB(+/-ALND)
| Study group | Role | What they receive |
|---|---|---|
| No SLNB group | Experimental | The study arm - BCS without SLNB Receives: Procedure: No axillary surgery |
| SLNB group | Other | The control arm - BCS with SLNB(+/-ALND) Receives: Procedure: Axillary surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive Disease Free Survival (iDFS)
Evaluate invasive disease free survivals
Measured: 5 years
Secondary outcomes (5)
Overall Survival (OS)
Evaluate overall survival
Measured: 5 years
Distant Metastasis Free Survival (DMFS)
Evaluate distant metastasis free survival
Measured: 5 years
Axillary recurrence rate
Evaluate ipsilateral axillary recurrence rate
Measured: 5 years
Locoregional Recurrence Rate (LRR)
Evaluate locoregional recurrence rate
Measured: 5 years
QoL
Evaluate Quality of Life of patient by EORTC QLQ-C30 questionnaire
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2024
- Study start4 Jun 2025
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 464 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Asan Medical Center
- Responsible party
- Principal investigator, Wonshik Han, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06704945
- Sponsor's protocol ID
- H-2410-138-1581
- Acronym
- Neo-NAUTILUS
- Status last verified
- Jan 2026
- First submitted
- 21 Nov 2024
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study protocol will be shared.
Publications
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.
PubMed 35184724Jung JJ, Kim HJ, Chae BJ, Kim EK, Ahn JH, Jeong J, Lee S, Jung SP, Woo J, Min J, Cheun JH, Chung MS, Shin KH, Chang JM, Moon WK, Han W. A Randomized Trial of Sentinel Node Biopsy Omission After Neoadjuvant Systemic Therapy in Clinically Node-Negative or Selected Node-Positive Breast Cancer. J Breast Cancer. 2025 Dec;28(6):437-447. doi: 10.4048/jbc.2025.0157. Epub 2025 Nov 14.
PubMed 41311332
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy: A Prospective, Phase III Clinical Trial
- ClinicalTrials.gov ID
- NCT06704945
- Acronym / sponsor ID
- Neo-NAUTILUS / H-2410-138-1581
- Keywords
- Omission of axillary surgery after neoadjuvant chemotherapy, Breast cancer, Neoadjuvant chemotherapy, De-escalation, Omission of surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 464 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Collaborators
- Asan Medical Center
- Study start
- 4 Jun 2025 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2034 (estimated)
- First posted
- 26 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
NEO-NAUTILUS is a prospective, multicenter, randomized phase III clinical trial to evaluate whether omitting axillary lymph node surgery (ALND or SLNB) in clinically lymph node-negative breast cancer patients after neoadjuvant chemotherapy is non-inferior to performing SLNB in terms of 5-year disease-free survival.
Detailed description
Background:
- No prospective studies have proven that axillary lymph node surgery improves survival in breast cancer patients.
- The ACOSOG Z0011 trial showed that additional axillary dissection did not improve recurrence or survival, even with a 23.7% incidence of non-sentinel node metastases.
- NSABP B-32 established the oncologic safety of SLNB, significantly reducing complications like lymphedema compared to axillary dissection. However, SLNB still carries risks of lymphedema, sensory changes, seromas, and infections.
- The trend has now shifted toward identifying candidates for omitting axillary surgery to minimize unnecessary complications.
- The SOUND trial demonstrated non-inferiority of omitting SLNB in early-stage breast cancer patients with negative axillary ultrasound. Five-year distant metastasis-free survival was comparable between SLNB and no-SLNB groups (97.7% vs. 98.0%).
- Improved ultrasound accuracy (e.g., FNR: 13.7% in SOUND; 11.3% in NAUTILUS) and the therapeutic contribution of whole-breast radiation likely support these findings.
- Patients with a complete pathological response (pCR) in the breast post-NAC rarely have residual lymph node metastases, reducing the need for axillary surgery.
- Single-arm studies (e.g., EUBREAST-01, ASICS, ASLAN) have explored omitting axillary surgery in patients with confirmed breast pCR. However, these studies face limitations due to small sample sizes, single-arm design, and the necessity of axillary surgery if pCR is not achieved.
- To address these limitations, the NEO-NAUTILUS trial proposes the first randomized trial to compare disease-free survival and local recurrence rates between patients who omit SLNB (experimental group) and those who undergo SLNB (control group) after NAC, focusing on patients deemed axillary node-negative by ultrasound.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No SLNB group | Experimental | Procedure: No axillary surgeryThe study arm - BCS without SLNB |
| SLNB group | Other | Procedure: Axillary surgeryThe control arm - BCS with SLNB(+/-ALND) |
Who may qualify
- Ages
- 19 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Women aged ≥19 years.
- Histologically confirmed invasive breast carcinoma treated with neoadjuvant chemotherapy.
- Clinical staging prior to NAC: cT1-3, cN0, M0 (AJCC 8th Edition).
- If pre-NAC staging is cT1-3, cN1, M0, must meet the following criteria:
- Negative axillary lymph node status on ultrasound after NAC.
Key exclusion criteria (7 listed)
- History of any cancer within the past 5 years.
- Bilateral breast cancer.
- Patients requiring mastectomy.
- Tumor size >5 cm after NAC.
- Male breast cancer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No axillary surgeryBCS only. Ommission of axillary surgery. No axillary surgery after neoadjuvant chemotherapy. | Procedure or surgery | No SLNB group |
| Axillary surgeryBCS with SLNB(+/-ALND) | Procedure or surgery | SLNB group |
Primary outcome
Invasive Disease Free Survival (iDFS)
Time frame: 5 years
Evaluate invasive disease free survivals
5 secondary outcomes
Overall Survival (OS)
Time frame: 5 years
Distant Metastasis Free Survival (DMFS)
Time frame: 5 years
Axillary recurrence rate
Time frame: 5 years
Locoregional Recurrence Rate (LRR)
Time frame: 5 years
QoL
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Background: PubMed 35184724Jung 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.
- Derived from this study: PubMed 41311332Jung JJ, Kim HJ, Chae BJ, Kim EK, Ahn JH, Jeong J, Lee S, Jung SP, Woo J, Min J, Cheun JH, Chung MS, Shin KH, Chang JM, Moon WK, Han W. A Randomized Trial of Sentinel Node Biopsy Omission After Neoadjuvant Systemic Therapy in Clinically Node-Negative or Selected Node-Positive Breast Cancer. J Breast Cancer. 2025 Dec;28(6):437-447. doi: 10.4048/jbc.2025.0157. Epub 2025 Nov 14.
- Individual participant dataSharing planned: Yes. Study protocol will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing No axillary surgery and Axillary surgery in people with Breast Cancer and Neoadjuvant Therapy, run by Seoul National University Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wonshik Han, MD, PhD. (82-2-3461-6060, hanw@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Invasive Disease Free Survival (iDFS) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06704945, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.