Hypofractionated Irradiation At Regional Nodal Area for Breast Cancer Vs Existed Standard Treatment

Breast Cancer Clinical Trial

— HARVEST  

Official title:

Hypofractionated Versus Conventional Intensity-Modulated Radiation Therapy for Breast Cancer Patients With an Indication for Regional Nodal Irradiation: A Randomized Multi-center Phase III Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03829553
• Other study ID #: RJBC-HFRNI
• Status: Recruiting
• Phase: Phase 3
• Start date: February 21, 2019
• Est. completion date: December 2027

Study information

• Verified date: May 2022
• Source: Ruijin Hospital
• Contact: Jia-Yi Chen
• Phone: +86-021-64370045
• Email: chenjiayi0188[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of this trial is to investigate the efficacy and safety of hypofractionated radiotherapy of 3 or 4 weeks by comparing with conventional radiotherapy of 5 or 6 weeks using intensity-modulated radiation therapy (IMRT) in breast cancer patients with an indication for regional nodal irradiation (RNI) following mastectomy or breast conserving surgery. Patients will be randomized to hypofractionated radiotherapy or conventional radiotherapy delivered to chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes). Eligible breast cancer patients will be followed for at least 5 years to evaluate the difference in 5-year locoregional recurrence, over survival, distant metastasis, toxicity and life quality between two groups.

Description:

Investigators hypothesize that hypofractionated radiotherapy is equally effective and safe as conventional radiotherapy in breast cancer patients with an indication for regional nodal irradiation. Eligible breast cancer patients are randomized 1:1 into the following two groups: hypofractionated radiotherapy of 2.67 Gy for 16 fractions (and sequential tumor bed boost of 2.67 Gy for 4 fractions in patients with intact breast) and conventional radiotherapy of 2Gy for 25 fractions (and sequential tumor bed boost of 2 Gy for 5 fractions in patients with intact breast). The dose was prescribed to ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes). All patients are treated with IMRT. The primary endpoint is locoregional recurrence. Patients will be followed at least 5 years after radiotherapy to evaluated over survival, distant metastasis, toxicity and life quality.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 801
• Est. completion date: December 2027
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria :

• Age 18-75 years old
• unilateral histologically confirmed invasive breast carcinoma of pT1-3
• breast conservation surgery or mastectomy
• Breast reconstruction is allowed
• histologically confirmed positive axillary lymph nodes (positive sentinel lymph nodes without axillary dissection is allowed)
• Life expectancy of >5 years
• A minimum negative surgical margin width of >2mm
• Karnofsky Performance Status =80
• Estrogen-receptor, Progesterone-receptor, human epidermal growth factor receptor-2 (HER-2) and Ki67 index can be performed on the primary breast tumor or axillary nodes.
• Written informed consent

Exclusion criteria:

• Supraclavicular lymph nodes, positive ipsilateral internal mammary lymph nodes or residual axillary nodes that may be eligible for a boost dose.
• Pregnant or lactating
• Severe non-neoplastic medical comorbidities
• Diagnosis of non-breast malignancy within 5 years preceding enrollment (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix).
• Simultaneous contralateral breast cancer
• Previous RT to thoracic and/or axillary, cervical region
• Active collagen vascular disease
• Evidence of distant metastatic disease and/or T4 disease

Notes for exlusion criteria:

1. Patients with severe non-neoplastic medical comorbidities (e.g.,severe ischemic heart disease, severe arrhythmia or severe chronic obstructive pulmonary disease ) that would preclude radiation treatment will be excluded.

2. Simultaneous contralateral breast cancer includes histologically confirmed DCIS only.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Radiation:
• Hypofractionated radiotherapy
4005 cGy/ 15 fractions / 3 weeks to ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes) and sequential tumor bed boost of 2.67Gy for 4 fractions in patients with intact breast
• Conventional radiotherapy
5000 cGy/ 25 fractions / 5 weeks ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular and internal mammary lymph nodes) and sequential tumor bed boost of 2Gy for 5 fractions in patients with intact breast

Locations

Country	Name	City	State
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai

Sponsors (9)

Lead Sponsor

Collaborator

Ruijin Hospital

Affiliated Hospital of Jiangnan University, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), RenJi Hospital, Shanghai 10th People's Hospital, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Zhongshan Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of Life-EORTC QLQ-C30	The time from the date of randomization to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-C30	1 years
Other	Quality of Life-EORTC QLQ-C30	The time from the date of randomization to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-C30	5 years
Other	Quality of Life-EORTC QLQ-BR23	The time from the date of randomization to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-BR23	1 years
Other	Quality of Life-EORTC QLQ-BR23	The time from the date of randomization to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-BR23	5 years
Primary	Locoregional recurrence (LRR)	any first recurrence confirmed by histology or cytology in the ipsilateral chest wall or breast or regional nodes areas (including axillary, supraclavicular, infraclavicular lymph nodes or IMN)	5 years
Secondary	Distant metastasis free survival (DMFS)	the time from the date of randomization to any recurrence of tumor at distant sites or death from any cause.	5 years
Secondary	Invasive recurrence-free survival (IRFS)	the time from the date of randomization to any invasive recurrence of tumor, distant metastases or death from any cause and second invasive primaries, including invasive neoplasms of the breast.	5 year
Secondary	over survival (OS)	the time from the date of randomization to the date of death from any cause or end of the follow-up.	5 years
Secondary	Number of Participants with excellent or good Cosmetic outcomes following breast conserving surgery-Harvard/NSABP/RTOG scoring scale	The time from the date of randomization to 5 years after completion of radiotherapy, the cosmetic outcomes will be evaluated before radiotherapy, every week during radiotherapy, 4 weeks after the last fraction received, every 6 months during the first 2 years and annually thereafter. The cosmetic outcomes are evaluated based on the Allegheny General Modification of the Harvard/(National Surgical Adjuvant Breast and Bowel Project) NSABP/ (Radiation Therapy Oncology Group) 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
Secondary	Number of Participants with =Grade1 Acute Radiation-induced Toxicity	within time from beginning of RT to 6 months after completion of RT assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.	6 months
Secondary	Number of Participants with =Grade1 Late Radiation-induced Toxicity	within time from 6 months after completion of RT to 5 years after completion of RT assessed according to the RTOG/ European Organization for Research on Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring Schema and CTCAE version 3.0	5 years
Secondary	Reconstruction complications	number of participants with any reconstruction complications (flap necrosis, capsular contracture, infection, loss of implant/expander or flaps, et al) and the interval between the RT and reconstruction complications will be recorded. Patient reported outcome with reconstruction will be evaluated by Breast-Q questionnaires before RT and 12 months after RT.	5 years