Ultra-Hypofractionated vs Moderate Hypofractionated Radiotherapy for Regional Lymph Nodes in High Risk Breast Cancer

NCT07527689 | Not Yet Recruiting DMC

• 1 other identifier: RJIBC-ULTRA RNI
• Study Type: interventional
• Target: 1,950
• Locations: 1 country
• Sites: 1

Brief Summary

For patients with breast cancer, regional nodal irradiation (RNI) can significantly reduce the risks of recurrence and mortality. Moderate hypofractionated regimens (40 to 42.5 Gy in 15 to 16 fractions over 3 weeks) is the established standard of care for RNI. Nevertheless, for the majority of patients, a three - week treatment duration is still regarded as lengthy. Although the ultra-hypofractionated regimen (26 Gy in 5 fractions over 1 week) has been proven non-inferior to the moderate hypofractionated regimen for whole breast irradiation, unambiguous evidence supporting its use in comprehensive RNI remains lacking, especially in high risk patients requiring internal mammary node irradiation (IMNI). This prospective, non-inferiority trial is designed to address this evidence gap by evaluating whether a one-week, ultra-hypofractionated regimen (26 Gy in 5 fractions) is non-inferior to the three-week regimen (40 Gy in 15 fractions) for comprehensive RNI, including IMNI.

Conditions

Breast Cancer

Keywords

Adjuvant Radiotherapy; regional nodal irradiation; internal mammary node irradiation; ultrahypofractionated radiation therapy; hypofractionated radiation therapy

Outcome Measures

Primary Outcomes (1)

• Invasive Breast Cancer Recurrence-Free Survival (IBC-RFS)

  IBC-RFS, defined as time from randomization until any first invasive ipsilateral breast, chest wall, regional, or distant recurrence, or death from breast cancer. Data for patients who are alive and free of an event at the time of final analysis or are lost to follow-up will be censored at the date of last contact.

  5 years

Secondary Outcomes (6)

• Acute Radiation-Induced Toxicity

  From start of radiotherapy through 90 days after completion of radiotherapy

• Late Radiation-Induced Toxicity

  From 90 days after completion of radiotherapy to 10 years

• Overall Survival (OS)

  10 years

• Locoregional Recurrence-Free Survival (LRRFS)

  10 years

• Distant Metastasis-Free Survival (DMFS)

  10 years

Other Outcomes (6)

• Second Primary Cancers

  10 years

• Health-Related Quality of Life (HRQoL)

  3, 6, 12, 24, 60 months

• Patients reported outcomes (PROs)

  3, 6, 12, 18, 24, 36,48, 60 months

Study Arms (2)

Ultra-hypofractionated regimen

EXPERIMENTAL

Participants will receive ultra-hypofractionated radiotherapy to regional lymph nodes and chest wall/whole breast. For patients after breast-conserving surgery, a sequential boost to the tumor bed will be administered. Systemic therapy (chemotherapy, endocrine therapy, or targeted therapy) will be given according to standard clinical practice.

Radiation: Ultra-hypofractionated Regional Nodal Irradiation

Moderate hypofractionated regimen

ACTIVE COMPARATOR

Participants will receive moderate hypofractionated radiotherapy to regional lymph nodes and chest wall/whole breast. For patients after breast-conserving surgery, a simultaneous integrated boost to the tumor bed will be administered. Systemic therapy (chemotherapy, endocrine therapy, or targeted therapy) will be given according to standard clinical practice.

Radiation: Moderate Hypofractionated Regional Nodal Irradiation

Interventions

Ultra-hypofractionated Regional Nodal Irradiation RADIATION

26 Gy in 5 fractions over 1 week (5.2 Gy per fraction, once daily). Treatment targets include ipsilateral supraclavicular, infraclavicular, internal mammary regions, chest wall or whole breast, and any portion of the undissected axilla at risk. Sequential tumor bed boost of 10.4 Gy in 2 fractions (5.2 Gy per fraction) for patients after breast-conserving surgery.

Also known as: 5-fraction Regional Nodal Irradiation, Ultra-hypofractionated RNI

Ultra-hypofractionated regimen

Moderate Hypofractionated Regional Nodal Irradiation RADIATION

40.05 Gy in 15 fractions over 3 weeks (2.67 Gy per fraction, once daily). Treatment targets include ipsilateral supraclavicular, infraclavicular, internal mammary regions, chest wall or whole breast, and any portion of the undissected axilla at risk. Simultaneous Integrated Boost of 48 Gy in 15 fractions (3.2 Gy per fraction) for patients after breast-conserving surgery.

Also known as: Moderate hypofractionated RNI, 15-fraction Regional Nodal Irradiation

Moderate hypofractionated regimen

Eligibility Criteria

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

You may qualify if:

• Provide a signed and dated informed consent form (ICF) before the initiation of any trial-specific procedures.
• Age ≥ 18 years.
• Histologically confirmed invasive breast cancer.
• Have received breast-conserving surgery or mastectomy with axillary staging, including sentinel lymph node biopsy, targeted axillary dissection and/or axillary lymph node dissection.
• Tumor stage is classified as T1, T2, or T3, as defined by the AJCC Cancer Staging Manual, 8th Edition.
• Meeting at least one of the following conditions:
• Pathological nodal status of pN2 or pN3a;
• Pathological nodal status of pN1 with one or more of the following high-risk factors:
• (I), Age \< 40 years. (II), Tumor location in the central or inner quadrant. (III), Estrogen Receptor (ER) negative. (IV), Presence of lymphovascular invasion (LVI). (V), Histological grade III. (VI), Patients presenting with clinical stage cN2-3a before neoadjuvant treatment.
• Pathologically negative surgical margins, defined as "no ink on tumor."
• Karnofsky Performance Status (KPS) score ≥ 80.
• Documented biomarker status for Estrogen Receptor (ER), Progesterone Receptor (PR), HER2, and Ki-67.
• Sufficient wound healing from surgery, with no signs of active infection at the intended radiation site.

You may not qualify if:

• Nodal stage is classified as N3b or N3c, as defined by the AJCC Cancer Staging Manual, 8th Edition.
• Has undergone or is planning immediate breast reconstruction with a permanent implant or tissue expander.
• Evidence of distant metastatic disease.
• Diagnosis of synchronous bilateral invasive breast cancer or a history of prior invasive cancer in either breast.
• History of prior radiation therapy to the chest, axillary, or supraclavicular regions.
• Known active collagen vascular diseases, particularly systemic lupus erythematosus or scleroderma, which are contraindications to radiotherapy.
• Presence of any severe, uncontrolled co-morbidity or medical condition that, in the investigator's judgment, would render the participant unsuitable for the study, compromise protocol compliance, or confound the interpretation of study results.
• History of any other malignancy within the 5 years before enrollment, with the exception of adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix.
• Participants who are pregnant or lactating at the time of study enrollment. (Note: In accordance with the standards of each participating institution, women of childbearing age are required to undergo pregnancy testing within 2 weeks prior to randomization.)

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Jia-Yi Chen, PhD, MD

  Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

• Lu Cao, PhD, MD

  Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lu Cao, PhD, MD

CONTACT

+86 147824551281; cl11879@rjh.com.cn

Jia-Yi Chen, PhD, MD

CONTACT

cjy11756@rjh.com.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: Professor

Model Details: Upon confirmation of eligibility and after obtaining informed consent, participants will be randomly assigned in a 1:1 ratio to either Arm A (Ultra-Hypofractionated regimen) or Arm B (Moderate hypofractionated regimen). To ensure a balance of key prognostic factors, randomization will be performed using a stratified block design, with stratification by pathologic nodal status (pN1 vs. pN2-3), and participating centers.

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 14, 2026
• Study Start: March 30, 2026
• Primary Completion (Estimated): March 30, 2034
• Study Completion (Estimated): March 30, 2039
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 12 months after publication and available for 5 years.
• Access Criteria: Proposals should be directed to cjy11756@rjh.com.cn. To gain access, requestors must: 1. Provide a methodologically sound research proposal 2. Obtain approval from their institutional ethics committee 3. Sign a data access and use agreement 4. Agree to use data only for the stated research purpose

Locations

CN (1)