Adjuvant Regional Nodal Radiation Therapy for One Week in Breast Cancer (ARROW)

One-week Hypofractionated Radiotherapy in Breast Cancer Patients With an Indication for Regional Nodal Irradiation: Prospective, Single-arm Trial

The purpose of this trial is to investigate the toxicities and efficacy of hypofractionated regional nodal radiotherapy (RNI) for one week in breast cancer patients treated with mastectomy or breast conserving surgery. Hypofractionated radiotherapy will be delivered to chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk). Eligible breast cancer patients will be followed for at least 1 years to evaluate the acute and late radiation-induced toxicities, locoregional recurrence, over survival, distant metastasis, and quality of life.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: External Beam radiotherapy using IMRT technique

Detailed Description

Eligible breast cancer patients will receive hypofractionated radiotherapy of 5.2 Gy in 5 fractions within one week and a sequential tumor bed boost of 5.2 Gy in 2 fractions to the conserved breast. The dose is prescribed to ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk). All patients are treated with intensity modulated radiation therapy (IMRT) technique. The primary endpoint is ≥2 grade any acute radiation induced toxicity event. patients will be followed for at least 1 years to evaluate the acute and late radiation-induced toxicity, locoregional recurrence, over survival, distant metastasis, and quality of life.

Calculation of the required number of cases based on an alpha of 0.05 and a power of 80% with a maximal tolerable toxicity difference of 10% during and within 6 months after RNI comparing to conventional radiotherapy and lost rate of follow up of 10%. In total 197 patients are needed to be recruited.

• Study Type: Interventional
• Enrollment (Anticipated): 197
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lu Cao, MD; Phone Number: 602400 +86-021-64370045; Email: caolu_163@ymail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiaotong University School Of Medicine
      • Contact: Lu Cao, MD, PhD; Phone Number: 602400 +86-021-64370045; Email: caolu_163@ymail.com
      • Principal Investigator: Jia-Yi Chen, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged >18 years old
• Underwent radical surgery with either mastectomy or breast conserving surgery and axillary lymph node dissection (ALND)
• Ipsilateral clinically diagnosed and histologically confirmed invasive breast cancer T1-3
• >=1 pathologically positive axillary lymph nodes
• Karnofsky Performance Status scoring ≥80, and anticipative overall survival >5 years
• Surgery wound healed without infection
• Negative pathologically surgical margin
• ER (estrogen-receptor), PR (progesterone-receptor), HER2 (human epidermal growth factor receptor 2) and Ki67 testing can be performed on the primary breast tumor
• Women of child-bearing potential must agree to use adequate contraception for up to 1 month before study treatment and the duration of study participation
• Ability to understand and willingness to participate the research and sign the consent forms

Exclusion Criteria:

• Pathologically positive ipsilateral supraclavicular lymph node
• Pathologically or radiologically confirmed involvement of ipsilateral internal mammary lymph nodes
• Pregnant or lactating women
• Severe non-neoplastic medical comorbidities
• History of non-breast malignancy within 5 years with the exception of lobular carcinoma in situ, basal cell carcinoma of the skin, carcinoma in situ of skin, Adenocarcinoma in situ of the lung and carcinoma in situ of the cervix
• simultaneous contralateral breast cancer
• Previous radiotherapy to the neck, chest and/or ipsilateral axillary region
• Active collagen vascular disease
• Definitive pathological or radiologic evidence of distant metastatic disease
• Primary T4 tumor
• Interval between radical surgery (mastectomy or breast conserving surgery) and radiotherapy was more than 12 weeks or interval between last dose of adjuvant chemotherapy and radiotherapy was more than 8 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypofractionated radiotherapy; Patients with an indication for regional nodal irradiation will receive 5.2 Gy in 5 fractions to chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk) and a sequential tumor bed boost of 5.2 Gy in 2 fractions to the conserved breast.	Radiation: External Beam radiotherapy using IMRT technique; 2600cGy/ 5 fractions / 1 weeks to ipsilateral chest wall or whole breast and regional lymph regions and a sequential tumor bed boost of 5.2 Gy in 2 fractions to the conserved breast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative complication rate of ≥Grade 2 Acute Radiation-induced Toxicity	Within time from the beginning of radiotherapy to 6 months after completion of radiotherapy, any acute radiation-induced toxicities will be assessed and recorded after the last fraction using the Common Terminology Criteria for Adverse Events (CTCAE) 3.0.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative complication rate of ≥Grade 2 Late Radiation-induced Toxicity	Within time from 6 months after completion of radiotherapy to 5 years after completion of radiotherapy, any late toxicity will be assessed and recorded using the Radiation Therapy Oncology Group (RTOG) /European Organization for Research on Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring Schema and CTCAE 3.0	5 years
Number of Participants with excellent or good Cosmetic outcomes following breast conserving surgery-Harvard/ NSABP/RTOG scoring scale	The cosmetic outcomes will be evaluated at 6 months after last fractions. The cosmetic outcomes are evaluated based on the Allegheny General Modification of the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/ RTOG scoring scale which graded patients into the following four classifications: excellent, when compared to the untreated breast, there is a minimal or no difference in the size or shape of the treated breast; good, slight difference in the size or shape of the treated breast; fair, obvious difference in the size or shape of the treated breast; and poor, marked change in the size or shape of the treated breast	6 months
Number of Participants with excellent or good Cosmetic outcomes following breast conserving surgery-Harvard/ NSABP/RTOG scoring scale	The cosmetic outcomes will be evaluated at 5 years after last fractions. The cosmetic outcomes are evaluated based on the Allegheny General Modification of the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/ RTOG scoring scale which graded patients into the following four classifications: excellent, when compared to the untreated breast, there is a minimal or no difference in the size or shape of the treated breast; good, slight difference in the size or shape of the treated breast; fair, obvious difference in the size or shape of the treated breast; and poor, marked change in the size or shape of the treated breast	5 years
Locoregional recurrence	any first recurrence confirmed by histology or cytology within the ipsilateral chest wall and/or regional nodes area(including supraclavicular, infraclavicular or internal mammary lymph nodes)	5 years
Distant metastasis free survival (DMFS)	The time from the date of enrollment to any recurrence of tumor at distant sites or death from any cause	5 years
Invasive recurrence-free survival (IRFS)	The time from the date of enrollment to any invasive recurrence of tumor or death from any cause	5 years
Over survival (OS)	The time from the date of enrollment to the date of death from any cause	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life-EORTC QLQ-C30	Quality of life will be assessed before radiotherapy and 6 months after last fractions using self administered questionnaire EORTC QLQ-C30	6 months
Quality of Life-EORTC BR-23	Quality of life will be assessed before radiotherapy and 6 months after last fractions using self administered questionnaire EORTC QLQ-BR23	6 months
Quality of Life-EORTC QLQ-C30	Quality of life will be assessed before radiotherapy and 5 years after last fractions using self administered questionnaire EORTC QLQ-C30	5 years
Quality of Life-EORTC BR-23	Quality of life will be assessed before radiotherapy and 5 years after last fractions using self administered questionnaire EORTC QLQ-BR23	5 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Lu Cao, MD, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2026

Study Registration Dates

• First Submitted: August 9, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 12, 2020

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: IMRT; regional nodal irradiation; Hypofractionated radiotherapy for one week
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: RJBC-SHF RNI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No