Level I–II axillary radiation versus whole regional nodal radiation after surgery for breast cancer with 1–2 sentinel-node macrometastases.

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

This will test whether limiting radiation to level I–II axillary lymph nodes works as well as whole regional nodal radiation for women with early breast cancer and 1–2 sentinel-node macrometastases.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 1608 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 15 sites (Guiyang, Guizhou and 14 other locations)
• Trial ID: NCT07469267 on ClinicalTrials.gov

What this trial studies

RELAX is an open-label, multicenter, randomized non-inferiority phase 3 trial that enrolls clinically node-negative breast cancer patients with one to two sentinel lymph node macrometastases. Participants are randomized 1:1 to receive either level I–II axillary irradiation plus breast/chest wall radiation or entire regional nodal irradiation including levels I–III and supraclavicular nodes, with internal mammary node irradiation optional for medial/central tumors. The primary endpoint is disease-free survival, with secondary endpoints including overall survival, regional and distant recurrence, radiation-related toxicities, and quality of life. Radiation must start within 12 weeks of surgery or the last adjuvant chemotherapy dose, and systemic therapies are given per tumor receptor status.

Who should consider this trial

Good fit: Adult women (≥18 years) with newly diagnosed invasive T1–3N0M0 breast cancer who had breast-conserving surgery or mastectomy, have one or two sentinel-node macrometastases (>2 mm) without further axillary dissection, ECOG 0–1, and who can start radiation within 12 weeks and receive indicated systemic therapy.

Not a fit: Patients with clinically node-positive disease, more than two positive axillary nodes, prior axillary dissection, poor performance status, or inability to receive standard systemic therapy are unlikely to benefit from this comparison.

Why it matters

Potential benefit: If successful, patients could receive less extensive regional radiation with similar cancer control, potentially reducing side effects and improving quality of life.

How similar studies have performed: Prior randomized trials (for example Z0011 and AMAROS) have shown it can be safe to avoid complete axillary dissection and that axillary radiation can control disease, but direct comparisons specifically limiting radiation to level I–II versus whole regional nodal irradiation are less well studied.

Eligibility criteria

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.

Where this trial is running

Guiyang, Guizhou and 14 other locations

• 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)

Study contacts

• Principal investigator: Xiaoli Yu, MD, PhD — Fudan University
• Study coordinator: Xiaoli Yu, MD, PhD

Conditions Breast Cancer; Radiotherapy; Sentinel Node Macrometastases; Regional Nodal Irradiation; Level I-II Axillary Irradiation