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

Official title

Axillary Radiotherapy or Axillary Lymph Node Dissection in Patients With Clinically Node- Positive Breast Cancer Undergoing Upfront Tailored Axillary Surgery: An International, Randomized Superiority Trial (OPBC-10/ NOAX)

Overview

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.

Detailed description

Despite major morbidity, axillary lymph node dissection (ALND) is standard of care in patients with clinically node positive breast cancer (cN+ BC) who undergo upfront surgery, which is frequently indicated in case of luminal biology. Tailored axillary surgery (TAS) was shown to selectively target positive nodes, thereby removing significantly more nodes than sentinel lymph node biopsy (SLNB), but less nodes than ALND. Therefore, it is currently unclear if TAS in combination with axillary radiotherapy (ART) exposes the axilla to less harm compared to ALND. It is hypothesized that patient's quality of life (QoL) and morbidity can be improved by replacing ALND with the combination of TAS and ART in patients undergoing upfront surgery.

The main goal of 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 QoL and occurrence of lymphedema two years after randomization.

Interventions

• Procedure Axillary lymph node dissection (ALND)
  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)
• Procedure Axillary radiotherapy (ART)
  Axillary irradiation

Primary outcome measures

• Change in arm-related Quality of Life (QoL) [Time frame: From baseline to 2 years after randomization]
• Occurrence of lymphedema [Time frame: From baseline to 2 years after randomization]

Eligibility criteria

Inclusion Criteria at screening:

• 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).
• Women of child-bearing potential are using effective contraception (condom, diaphragm, intrauterine device), are not pregnant or lactating and agree not to become pregnant during trial treatment (until end of RT) and thereafter during the time recommended by the guidelines - also for adjuvant systemic therapies. A negative pregnancy test before registration is required for all women of child-bearing potential.
• Men agree not to father a child during trial treatment and for 6 months afterward.

Exclusion criteria at screening:

• 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.

Exclusion criteria at randomization (intraoperatively):

• Absence of clip in the specimen radiography.
• Palpable disease left behind in the axilla after TAS.
• No SLN identified in the axilla.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Switzerland · 24 centers

• Kantonsspital Baden — Baden
• Breast Surgery Service, University Hospital Basel — Basel
• University Hospital of Bern (Inselspital) — Bern
• Clinique des Grangettes — Chêne-Bougeries
• Graubünden Cantonal Hospital — Chur
• Spital Thurgau — Frauenfeld
• Hôpitaux Universitaires de Genève — Geneva
• Clinique de Genolier — Genolier
• … and 16 more centers

Austria · 6 centers

• KH Dornbirn — Dornbirn
• LKH Feldkirch — Feldkirch
• MUI - Univ. Klinik f. Frauenheilkunde Innsbruck — Innsbruck
• Ordensklinikum Linz — Linz
• Medical University Vienna, Department of Gynecology — Vienna
• Medical University Vienna, Department of Surgery — Vienna

Ireland · 6 centers

• Cork University Hospital — Cork
• Beaumont Hospital Dublin — Dublin
• St- Luke's Hospital Dublin — Dublin
• St. James's Hospital Dublin — Dublin
• St. Vincent's University Hospital — Dublin
• University Hospital Galway — Galway

United States · 4 centers

• Walter Reed National Military Medical Center — Bethesda
• Duke University/Duke Cancer Center — Durham
• Fox Chase Cancer Center — Philadelphia
• Swedish Cancer Institute — Seattle

Germany · 4 centers

• University Hospital Heidelberg, Women's Clinic — Heidelberg
• Brustzentrum Heidelberg Klinik St. Elisabeth GmbH — Heidelberg
• Breast Center Osnabrück — Osnabrück
• HELIOS Universitätsklinikum Wuppertal — Wuppertal

Greece · 3 centers

• "Alexandra" Hospital, Athens — Athens
• University Hospital of Heraklion — Heraklion
• University Hospital of Larissa — Larissa

Italy · 2 centers

• Istituto Oncologico Veneto IRCCS — Padova
• Policlinico Universitario "Agostino Gemelli — Rome

Turkey (Türkiye) · 2 centers

• İstanbul Bağcılar Training and Research Hospital — Istanbul
• Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital — Istanbul

Canada · 1 center

• CIUSSS du Centre Ouest-de-l 'Ile-de-Montréal — Montreal

Croatia · 1 center

• Breast Centre of Clinical Hospital, Rijeka — Rijeka

Latvia · 1 center

• Pauls Stradiņš Clinical University Hospital — Riga

Identifiers

NCT: NCT07140172 · 2025-01460; NOAX; bb24Weber2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗