Level I-II Axillary Irradiation in Breast Cancer With Sentinel-Node Macro-metastases (RELAX)

March 10, 2026 updated by: Xiaoli Yu, Fudan University

Entire Regional Nodal Irradiation vs. Level I-II Axillary Irradiation in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macro-metastases (RELAX)：A Prospective, Multicenter, Randomized, Phase 3 Clinical Trial

The RELAX trial is an open-label, multicenter, non-inferiority, randomized, phase 3 clinical trial.

Multiple randomized trials have demonstrated the safety of omitting complete axillary-lymph-node dissection in patients with invasive breast cancer and limited sentinel lymph node metastases. However, the necessity and optimal extent of regional nodal irradiation remains uncertain. The aim of this study is to evaluate whether level I-II axillary irradiation is non-inferior to whole regional nodal irradiation in terms of disease-free survival in clinically node-negative breast cancer patients with 1-2 sentinel lymph node macro-metastases.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJIECTIVE:

To evaluate whether level I-II axillary irradiation is non-inferior to whole regional nodal irradiation in terms of disease-free survival in clinically node-negative breast cancer patients with 1-2 sentinel lymph node macro-metastases.

SECONDARY OBJECTIVES:

I. to estimate the difference of overall survival; II. to estimate the difference of ipsilateral regional recurrence; III. to estimate the difference of ipsilateral local regional recurrence; IV. to estimate the difference of distant recurrence; V. to estimate the difference of radiation related toxicities and quality of life.

Outline: Patients are randomized in a 1:1 ratio to two treatment arms.

Arm A (Level I-II axillary irradiation): Radiation is delivered to the breast after breast conserving surgery(BCS) or chest wall after mastectomy, level I-II axillary lymph nodes. Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.

Arm B (Entire regional nodal irradiation): Radiation is delivered to the breast after BCS or chest wall after mastectomy, whole axillary lymph nodes (levels I-III) and supraclavicular lymph nodes. IMN is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.

Study Type

Interventional

Enrollment (Estimated)

1608

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 Contact

Study Contact Backup

Study Locations

  • China
    • Guizhou
      • Guiyang, Guizhou, China
        • Not yet recruiting
        • Oncology Department, Guizhou Provincial People's Hospital
        • Principal Investigator:
          • Yong Li
        • Contact:
    • Hebei
      • Shijiazhuang, Hebei, China
        • Not yet recruiting
        • The Fourth Hospital of Hebei Medical University
        • Contact:
        • Principal Investigator:
          • Zhikun Liu
    • Heilongjiang
      • Harbin, Heilongjiang, China
        • Not yet recruiting
        • Harbin medical university cancer hospital
        • Contact:
        • Principal Investigator:
          • Qingyong Xu
    • Hubei
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
        • Principal Investigator:
          • Tengfei Chao
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Department of Radiation and Medical Oncology，Zhongnan Hospital of Wuhan University
        • Principal Investigator:
          • Haijun Yu
        • Contact:
    • Hunan
      • Changde, Hunan, China
        • Not yet recruiting
        • Changde Hospital, Xiangya school of Medicine, Central South University (The first people's hospital of Changde city)
        • Principal Investigator:
          • Tao Wu
        • Contact:
      • Changsha, Hunan, China
        • Not yet recruiting
        • Hunan cancer hospital/The affiliated cancer hospital of xiangya school of medicine,Central South university
        • Principal Investigator:
          • Hui Wang
        • Contact:
    • Liaoning
      • Dalian, Liaoning, China
        • Not yet recruiting
        • Department of Radiation and Medical Oncology, Affiliated Zhongshan Hospital of Dalian University
        • Contact:
        • Principal Investigator:
          • Zhe Wang
    • Shandong
      • Jinan, Shandong, China
        • Not yet recruiting
        • Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital)
        • Contact:
        • Principal Investigator:
          • Wei Huang
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Xiaoli Yu
      • Shanghai, Shanghai Municipality, China
        • Not yet recruiting
        • Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
        • Contact:
        • Principal Investigator:
          • Chunling Jiang
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China
        • Not yet recruiting
        • Tianjin Medical University Cancer Institute and Hospital
        • Principal Investigator:
          • Jing Wang
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Not yet recruiting
        • Zhejiang Cancer Hospital
        • Contact:
        • Principal Investigator:
          • Xia Zhou
      • Hangzhou, Zhejiang, China
        • Not yet recruiting
        • The Second Affiliated Hospital of Zhejiang University
        • Contact:
        • Principal Investigator:
          • Ting Zhang
      • Ningbo, Zhejiang, China
        • Not yet recruiting
        • Department of Chemoradiation Oncology, The Affiliated Lihuili Hospital of Ningbo University
        • Contact:
        • Principal Investigator:
          • Kaitai Liu

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Female ≥ 18 years of age;
  2. Newly diagnosed primary invasive breast cancer;
  3. Clinically stage T1-3N0M0;
  4. Patients received surgery as first treatment,and have undergone breast conserving-surgery or mastectomy (with or without breast reconstruction) with negative margins;
  5. Have one or two macrometastases (>2 mm) at sentinel lymph node biopsy,and without further axillary lymph node dissection;
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
  7. Will receive endocrine therapy for at least 5 years for estrogen receptor (ER) and/or progesterone receptor (PR) positive patients; will receive anti-HER2 (human epidermal growth factor receptor 2) therapy for 1 year for HER2 positive patients;
  8. Radiation therapy must begin no later than 12 weeks after the last dose of adjuvant chemotherapy or the last breast cancer surgery if no adjuvant chemotherapy;
  9. Patients have adequate organ function;
  10. Acquirement of informed consent.

Exclusion Criteria:

  1. Patients have received neoadjuvant systemic therapy;
  2. Clinical stage T4 or IV (metastatic) breast cancer, or presence of regional metastases before surgery;
  3. History of any prior ipsilateral or contralateral invasive breast cancer, history of other malignancies except for appropriately treated skin basal cell carcinoma and cervical carcinoma in situ;
  4. History of previous radiotherapy towards the ipsilateral chest/lymph nodes.
  5. The ipsilateral axillary lymph node dissection or other previous axillary surgery;
  6. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, or psychiatric disease), inability to tolerate radiotherapy or systemic therapy if indicated;
  7. Current pregnancy and/or lactation;
  8. Inability or unwillingness to comply with protocol requirements.

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: Entire regional nodal irradiation
Radiation is delivered to the breast after BCS or chest wall after mastectomy, whole axillary lymph nodes (levels I-III) and supraclavicular lymph nodes. Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.
Radiation: Entire regional nodal irradiation

Radiation is delivered to the breast after BCS or chest wall after mastectomy, whole axillary lymph nodes (levels I-III) and supraclavicular lymph nodes. Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.

Both hypofractionated and conventional fractionated radiation therapy are permitted: the conventional fractionated regimen is 50 Gy in 25 fractions of 2 Gy; the hypofractionated schedule is 42.56 Gy in 16 fractions of 2.66 Gy after mastectomy, or 40.05 Gy in 15 fractions of 2.67 Gy after breast-conserving surgery. Tumor bed after breast-conserving surgery is at the discretion of the treating physician, boost doses will be 10~16 Gy in 5~8 fractions of 2 Gy or 10.68~16.2 Gy in 4~6 fractions of 2.67 Gy.
Experimental: Level I-II axillary irradiation
Radiation is delivered to the breast after BCS or chest wall after mastectomy and low axillary lymph nodes (levels I-II). Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.
Radiation: Level I-II axillary irradiation

Radiation is delivered to the breast after BCS or chest wall after mastectomy and low axillary lymph nodes (levels I-II). Internal mammary nodes(IMN) is optional and it is recommended to irradiate IMN when the tumor is located in the medial or central quadrant.

Both hypofractionated and conventional fractionated radiation therapy are permitted: the conventional fractionated regimen is 50 Gy in 25 fractions of 2 Gy; the hypofractionated schedule is 42.56 Gy in 16 fractions of 2.66 Gy after mastectomy, or 40.05 Gy in 15 fractions of 2.67 Gy after breast-conserving surgery. Tumor bed after breast-conserving surgery is at the discretion of the treating physician, boost doses will be 10~16 Gy in 5~8 fractions of 2 Gy or 10.68~16.2 Gy in 4~6 fractions of 2.67 Gy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival (DFS)
Time Frame: 5 years
Defined as time from randomization until to local, regional, or distant recurrence, or any death, or secondary primary cancer.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 5 years
Defined as the time from randomization to death from any cause.
5 years
Regional Recurrence (RR)
Time Frame: 5 years
Defined as the time from randomization to the date of the first ipsilateral axillary, supraclavicular, or internal mammary nodal recurrence.
5 years
Local Regional Recurrence (LRR)
Time Frame: 5 years
Defined as the time from randomization to the date of the first ipsilateral breast, chest wall, axillary, supraclavicular, or internal mammary nodal recurrence.
5 years
Distance Recurrence (DR)
Time Frame: 5 years
Defined as the time from randomization to the date of the first distant breast cancer recurrence.
5 years
Safety outcomes
Time Frame: 5 years
The frequency and severity of acute and late radiation-related adverse events are assessed and graded based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. For some events that CTCAE grading are not available, RTOG/the European Organization for Research and Treatment of Cancer (EORTC) late radiation morbidity scale and LENT-SOMA criteria are used.
5 years
Patient-reported outcomes
Time Frame: 5 years
Assessment of treatment-related symptoms, health-related quality of life via three questionnaires, including the EORTC Quality of Life Questionnaire (EORTC-QLQ-C30; version 3), breast cancer module (QLQ-BR23) and upper limb function via the Quick Disabilities of the Arm, Shoulder and Hand (q-DASH) questionnaire.
5 years

Collaborators and Investigators

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

Sponsor

Fudan University

Investigators

  • Principal Investigator: Xiaoli Yu, MD, PhD, Fudan University
  • Principal Investigator: Zhaozhi Yang, MD, PhD, Fudan University

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)

October 24, 2025

Primary Completion (Estimated)

December 31, 2032

Study Completion (Estimated)

December 31, 2035

Study Registration Dates

First Submitted

February 8, 2026

First Submitted That Met QC Criteria

March 10, 2026

First Posted (Actual)

March 13, 2026

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FDRT-BC026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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