NCT07469267

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,608

participants targeted

Target at P75+ for not_applicable breast-cancer

Timeline
117mo left

Started Oct 2025

Longer than P75 for not_applicable breast-cancer

Geographic Reach
1 country

15 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress6%
Oct 2025Dec 2035

Study Start

First participant enrolled

October 24, 2025

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

February 8, 2026

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 13, 2026

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2032

Expected
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2035

Last Updated

March 13, 2026

Status Verified

February 1, 2026

Enrollment Period

7.2 years

First QC Date

February 8, 2026

Last Update Submit

March 10, 2026

Conditions

Breast CancerRadiotherapy

Keywords

Breast CancerSentinel Node MacrometastasesRegional Nodal IrradiationLevel I-II Axillary Irradiation

Outcome Measures

Primary Outcomes (1)

  • Disease Free Survival (DFS)

    Defined as time from randomization until to local, regional, or distant recurrence, or any death, or secondary primary cancer.

    5 years

Secondary Outcomes (6)

  • Overall survival (OS)

    5 years

  • Regional Recurrence (RR)

    5 years

  • Local Regional Recurrence (LRR)

    5 years

  • Distance Recurrence (DR)

    5 years

  • Safety outcomes

    5 years

  • +1 more secondary outcomes

Study Arms (2)

Entire regional nodal irradiation

ACTIVE COMPARATOR

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

Level I-II axillary irradiation

EXPERIMENTAL

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

Interventions

Entire regional nodal irradiationRADIATION

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.

Entire regional nodal irradiation
Level I-II axillary irradiationRADIATION

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.

Level I-II axillary irradiation

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Female ≥ 18 years of age;
  • Newly diagnosed primary invasive breast cancer;
  • Clinically stage T1-3N0M0;
  • Patients received surgery as first treatment,and have undergone breast conserving-surgery or mastectomy (with or without breast reconstruction) with negative margins;
  • Have one or two macrometastases (\>2 mm) at sentinel lymph node biopsy,and without further axillary lymph node dissection;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
  • 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;
  • 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;
  • Patients have adequate organ function;
  • Acquirement of informed consent.

You may not qualify if:

  • Patients have received neoadjuvant systemic therapy;
  • Clinical stage T4 or IV (metastatic) breast cancer, or presence of regional metastases before surgery;
  • 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;
  • History of previous radiotherapy towards the ipsilateral chest/lymph nodes.
  • The ipsilateral axillary lymph node dissection or other previous axillary surgery;
  • 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;
  • Current pregnancy and/or lactation;
  • Inability or unwillingness to comply with protocol requirements.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Oncology Department, Guizhou Provincial People's Hospital

Guiyang, Guizhou, China

NOT YET RECRUITING

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

NOT YET RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

NOT YET RECRUITING

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

NOT YET RECRUITING

Department of Radiation and Medical Oncology，Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

NOT YET RECRUITING

Changde Hospital, Xiangya school of Medicine, Central South University (The first people's hospital of Changde city)

Changde, Hunan, China

NOT YET RECRUITING

Hunan cancer hospital/The affiliated cancer hospital of xiangya school of medicine,Central South university

Changsha, Hunan, China

NOT YET RECRUITING

Department of Radiation and Medical Oncology, Affiliated Zhongshan Hospital of Dalian University

Dalian, Liaoning, China

NOT YET RECRUITING

Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute,Shandong Cancer Hospital)

Jinan, Shandong, China

NOT YET RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

RECRUITING

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

NOT YET RECRUITING

The Second Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

NOT YET RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

NOT YET RECRUITING

Department of Chemoradiation Oncology, The Affiliated Lihuili Hospital of Ningbo University

Ningbo, Zhejiang, China

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Xiaoli Yu, MD, PhD

    Fudan University

    PRINCIPAL INVESTIGATOR

  • Zhaozhi Yang, MD, PhD

    Fudan University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoli Yu, MD, PhD

CONTACT

+86-13817893133xiaoliyu@fudan.edu.cn

Li Zhang, M.D.

CONTACT

+86-18121299516lizhang_@fudan.edu.cn

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of the Department of Radiation Oncology, Fudan University Shanghai Cancer Center

Study Record Dates

First Submitted

February 8, 2026

First Posted

March 13, 2026

Study Start

October 24, 2025

Primary Completion (Estimated)

December 31, 2032

Study Completion (Estimated)

December 31, 2035

Last Updated

March 13, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations

CN(15)