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

Official title

A Multicenter, Randomized, Controlled Phase III Clinical Trial Comparing Ultra-Hypofractionated Versus Moderate Hypofractionated Radiotherapy for Regional Lymph Nodes in Post-operative Breast Cancer

Overview

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.

Detailed description

The study intervention is RNI delivered using modern techniques, including Intensity-Modulated Radiation Therapy (IMRT), Volumetric Modulated Arc Therapy (VMAT) or Intensity-Modulated Proton Therapy (IMPT). Technical parameters for treatment delivery, such as target delineation and OARs dose constraints, will be standardized across both arms. The investigational component is the randomized comparison of the ultra-hypofractionated regimen (26 Gy in 5 fractions over one week) and the moderate hypofractionated regimen (40 Gy in 15 fractions over three weeks).

Interventions

• Radiation Ultra-hypofractionated Regional Nodal Irradiation
  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.
• Radiation Moderate Hypofractionated Regional Nodal Irradiation
  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.

Primary outcome measures

• Invasive Breast Cancer Recurrence-Free Survival (IBC-RFS) [Time frame: 5 years]

Secondary outcome measures (6)

• Acute Radiation-Induced Toxicity [Time frame: From start of radiotherapy through 90 days after completion of radiotherapy]
• Late Radiation-Induced Toxicity [Time frame: From 90 days after completion of radiotherapy to 10 years]
• Overall Survival (OS) [Time frame: 10 years]
• Locoregional Recurrence-Free Survival (LRRFS) [Time frame: 10 years]
• Distant Metastasis-Free Survival (DMFS) [Time frame: 10 years]
• Disease-Free Survival (DFS) [Time frame: 10 years]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.)

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

China · 1 center

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai

Identifiers

NCT: NCT07527689 · RJIBC-ULTRA RNI

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗