Axillary Radiotherapy or Axillary Lymph Node Dissection in Patients With Clinically Node- Positive Breast Cancer Undergoing Upfront Tailored Axillary Surgery

NCT07140172 | Recruiting DMC

• 1 other identifier: 2025-01460; NOAX; bb24Weber2
• Study Type: interventional
• Target: 1,060
• Locations: 11 countries
• Sites: 54

Brief Summary

This trial is to investigate if in patients with clinically node positive breast cancer undergoing upfront surgery, treatment with TAS and ART is superior to ALND in terms of arm-related Quality of Life (QoL) and occurrence of lymphedema two years after randomization.

Conditions

Breast Cancer

Keywords

axillary lymph node dissection (ALND); axillary radiotherapy (ART); tailored axillary surgery (TAS); clinically node positive breast cancer (cN+ BC); sentinel lymph node biopsy (SLNB); Breast cancer-specific survival (BCSS); NOAX; OPBC-10; Lymphedema; Quality of life (QoL)

Outcome Measures

Primary Outcomes (2)

• Change in arm-related Quality of Life (QoL)

  The arm subscale (ARM) of the FACT-B+4 is used to assess arm-related QoL.The FACT-B comprises five subscales: physical well-being (seven items), social well-being (seven items), emotional well-being (six items), functional well-being (seven items), and concerns specific to patients with breast cancer (13 items). The FACT-B+4 questionnaire consists of the FACT-B subscales and the additional ARM subscale including five questions related to arm morbidity with four additional validated arm morbidity items that are added to the one item on arm morbidity already included in the FACT-B questionnaire. Patients are asked to indicate on a five- point scale from 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), to 4 (very much), to what degree each statement applied over the previous 7 days. The individual scoring of each question is inverted and added up to the total score ranging between 0 and 20 points, higher scores representing less arm problems.

  From baseline to 2 years after randomization

• Occurrence of lymphedema

  Bilateral measurements will be obtained 10 cm above and 5 cm below the olecranon process on both the ipsilateral and contralateral upper extremities. The change in ipsilateral upper- extremity circumference, corrected for any change in the contralateral upper extremity, will be calculated using the following formula: L = (Ia - Ib) - (Ca- Cb). It indicates ipsilateral upper-extremity circumference, C indicates contralateral upper- extremity circumference, a indicates assessments during trial treatment and follow-up, and b indicates baseline assessment. L will be calculated for both upper arm and forearm, and lymphedema is defined as present if L \> 2 cm for either location. The proportion of patients with lymphedema will be calculated.

  From baseline to 2 years after randomization

Study Arms (2)

Arm A (Control): ALND

ACTIVE COMPARATOR

1. Surgery: Tailored Axillary Surgery (TAS) includes the sentinel lymph node (SLN) procedure, radiographic confirmation of the removal of previously marked lymph nodes (clip removal), and the targeted excision of palpably suspicious lymph nodes. 2. Surgery: ALND - current standard of care, with the intention to remove the entire soft tissue within the anatomical borders of the axilla. 3. Radiotherapy: All patients receive adjuvant breast irradiation following breast-conserving surgery, along with extended regional lymph node irradiation (breast/chest wall irradiation excluding the axilla).

Procedure: Axillary lymph node dissection (ALND)

Arm B (Investigational): ART

ACTIVE COMPARATOR

1. Surgery: Tailored Axillary Surgery (TAS) includes the sentinel lymph node (SLN) procedure, radiographic confirmation of the removal of previously marked lymph nodes (clip removal), and the targeted excision of palpably suspicious lymph nodes. 2. Radiotherapy: All patients receive adjuvant breast irradiation following breast-conserving surgery, along with extended regional lymph node irradiation (breast/chest wall irradiation excluding the axilla).TAS + breast/chest wall and axillary irradiation (ART) 3. Radiotherapy: Axillary radiotherapy (ART).

Procedure: Axillary radiotherapy (ART)

Interventions

Axillary lymph node dissection (ALND) PROCEDURE

Surgical removal of lymphatic tissue within the anatomical boundaries of the axilla (standard of care in the upfront surgery setting in patients with cN+ BC)

Arm A (Control): ALND

Axillary radiotherapy (ART) PROCEDURE

Axillary irradiation

Arm B (Investigational): ART

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent according to ICH/GCP regulations prior to any trial specific procedures.
• Patients ≥ 18 years of age.
• Node-positive breast cancer (histologically or cytologically proven both in primary tumor and in lymph node) American Joint Committee on Cancer/ International Union Against Cancer (AJCC/UICC) stage II-III (all molecular subtypes allowed).
• Node-positivity detected by imaging and non-palpable (iN+) and confirmed by pathology.
• Node-positivity palpable (cN1-3) and confirmed by pathology.
• Occult breast cancer is allowed, if biopsy-proven axillary lymphatic metastasis is present.
• Eligible for primary ALND or SLN procedure and either:
• Newly diagnosed.
• Isolated in-breast recurrence or second ipsilateral breast cancer after previous breast conserving surgery and sentinel procedure and at least 3 years disease free and no prior axillary dissection or axillary RT.
• Upfront surgery setting.
• Most suspicious axillary lymph node clipped. (If clipping is not part of the routine, this should be done after consent of the patient as a study procedure.)
• Ability to complete the QoL questionnaires.
• WHO performance status 0-2
• Adequate condition for general anesthesia, breast cancer surgery and radiotherapy.
• Adult patients (≥18 years of age).

You may not qualify if:

• Stage IV breast cancer.
• Clinical N3c breast cancer without axillary disease (clinical N3a and clinical N3b are allowed).
• Clinical N2b breast cancer (clinical N2a is allowed).
• Contralateral breast cancer within 3 years.
• Prior axillary surgery (except prior sentinel node procedure in case of in-breast recurrence).
• Prior regional radiotherapy.
• Neoadjuvant treatment with the exception of bridging therapy given for less than 3 months.
• History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from pre-registration with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
• Absence of clip in the specimen radiography.
• Palpable disease left behind in the axilla after TAS.
• No SLN identified in the axilla.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (54)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20814, United States

NOT YET RECRUITING

Duke University/Duke Cancer Center

Durham, North Carolina, 27710, United States

NOT YET RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

NOT YET RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

NOT YET RECRUITING

KH Dornbirn

Dornbirn, Austria

NOT YET RECRUITING

LKH Feldkirch

Feldkirch, Austria

NOT YET RECRUITING

MUI - Univ. Klinik f. Frauenheilkunde Innsbruck

Innsbruck, Austria

RECRUITING

Ordensklinikum Linz

Linz, Austria

NOT YET RECRUITING

Medical University Vienna, Department of Gynecology

Vienna, Austria

NOT YET RECRUITING

Medical University Vienna, Department of Surgery

Vienna, Austria

NOT YET RECRUITING

CIUSSS du Centre Ouest-de-l 'Ile-de-Montréal

Montreal, Canada

NOT YET RECRUITING

Breast Centre of Clinical Hospital, Rijeka

Rijeka, Croatia

NOT YET RECRUITING

University Hospital Heidelberg, Women's Clinic

Heidelberg, 69120, Germany

RECRUITING

Brustzentrum Heidelberg Klinik St. Elisabeth GmbH

Heidelberg, Germany

RECRUITING

Breast Center Osnabrück

Osnabrück, Germany

NOT YET RECRUITING

HELIOS Universitätsklinikum Wuppertal

Wuppertal, Germany

NOT YET RECRUITING

"Alexandra" Hospital, Athens

Athens, Greece

NOT YET RECRUITING

University Hospital of Heraklion

Heraklion, Greece

NOT YET RECRUITING

University Hospital of Larissa

Larissa, Greece

NOT YET RECRUITING

Cork University Hospital

Cork, Ireland

NOT YET RECRUITING

Beaumont Hospital Dublin

Dublin, Ireland

NOT YET RECRUITING

St- Luke's Hospital Dublin

Dublin, Ireland

NOT YET RECRUITING

St. James's Hospital Dublin

Dublin, Ireland

NOT YET RECRUITING

St. Vincent's University Hospital

Dublin, Ireland

NOT YET RECRUITING

University Hospital Galway

Galway, Ireland

NOT YET RECRUITING

Istituto Oncologico Veneto IRCCS

Padova, Italy

NOT YET RECRUITING

Policlinico Universitario "Agostino Gemelli

Rome, Italy

NOT YET RECRUITING

Pauls Stradiņš Clinical University Hospital

Riga, Latvia

NOT YET RECRUITING

Kantonsspital Baden

Baden, Switzerland

RECRUITING

Breast Surgery Service, University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

University Hospital of Bern (Inselspital)

Bern, Switzerland

NOT YET RECRUITING

Clinique des Grangettes

Chêne-Bougeries, 1224, Switzerland

RECRUITING

Graubünden Cantonal Hospital

Chur, Switzerland

RECRUITING

Spital Thurgau

Frauenfeld, 8500, Switzerland

RECRUITING

Hôpitaux Universitaires de Genève

Geneva, Switzerland

RECRUITING

Clinique de Genolier

Genolier, Switzerland

RECRUITING

Hirslandenklinik St. Anna

Lucerne, Switzerland

RECRUITING

Kantonsspital Luzern

Lucerne, Switzerland

RECRUITING

Centro di Senologia della Svizzera Italiana

Lugano, Switzerland

RECRUITING

Ticino Breast Center

Lugano, Switzerland

NOT YET RECRUITING

Hôpital Neuchâtelois

Neuchâtel, Switzerland

RECRUITING

Bethesda Hospital Basel

Pratteln, Switzerland

NOT YET RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

NOT YET RECRUITING

Tumor-& Brustzentrum Ostschweiz St. Gallen

Sankt Gallen, Switzerland

RECRUITING

Schaffhausen Cantonal Hospital

Schaffhausen, Switzerland

RECRUITING

Spital Limmattal

Schlieren, Switzerland

RECRUITING

Hôpital du Valais, Hôpital de Sion

Sion, Switzerland

RECRUITING

Kantonsspital Winterthur

Winterthur, Switzerland

RECRUITING

Spital Zollikerberg

Zollikerberg, Switzerland

RECRUITING

Brustzentrum Zürich (Seefeld)

Zurich, 8008, Switzerland

RECRUITING

Stadtspital Triemli

Zurich, Switzerland

RECRUITING

University Hospital Zürich

Zurich, Switzerland

NOT YET RECRUITING

İstanbul Bağcılar Training and Research Hospital

Istanbul, Turkey (Türkiye)

NOT YET RECRUITING

Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital

Istanbul, Turkey (Türkiye)

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Lymphedema

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Walter P. Weber, Prof. Dr. med.

  Breast Surgery Service, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Walter P. Weber, Prof. Dr. med.

CONTACT

+41 61 328 61 49; walter.weber@usb.ch

OPBC project management team

CONTACT

+41 61 55 65134; noax.trial@usb.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: International, multicenter, randomized controlled, superiority trial comparing TAS and ART (experimental group) to ALND (control group) in terms of arm-related QoL and occurrence of lymphedema two years after randomization (co-primary endpoints).

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: August 24, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 1, 2037
• Last Updated: May 11, 2026

Record last verified: 2026-05

Locations

IE (6); LA (1); US (4); TU (2); IT (2); CA (1); AU (6); DE (4); CR (1); CH (24); GR (3)