Clinical trial NCT04025164: Hypofractionated Vs Conventional Fractionated Radiotherapy After Breast Conserving Surgery
Official title: Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast Conserving Surgery：a Multi-center Phase III Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Hypofractionated radiotherapy
Breast Conserving Surery
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2019-07-18
Enrollment: 4052
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study was designed to investigate whether hypofractionated radiotherapy(HF-RT) is noninferior to conventionally fractionated radiotherapy (CF-RT) in terms of tumor loco-regional control for patients after breast conserving surgery

Detailed description: Eligible patients after breast conserving surgery will be randomized 1:1 into hypofractionated radiotherapy (HF-RT) group or conventionally fractionated radiotherapy (CF-RT) group.

Patients in HF-RT group will receive 40 Gy/15 fractions irradiation to the whole breast with/without regional lymphnodes within 3 weeks and the tumor bed is boosted to 48 Gy/15 fractions simutaneously.

Patients in CF-RT group will receive 50 Gy/ 25 fractions irradiation to whole breast with/without regional lymphnodes within 5 weeks and the tumor bed is boosted to 60 Gy/30 fractions sequentially.

The primary endpoint is loco-regional recurrence. Other cancer related events and acute/late radiation morbidities will also be evaluated. The patients will be followed for 10 years.

It is hypothesized that hypofractionated radiotherapy is non inferior to conventional fractionated radiotherapy in terms of tumor loco-regional control for patients after breast conserving surgery.

Eligibility criteria: Inclusion Criteria:

* Female
* Age18-70 years
* Imaging examination confirmed single lesion. if the tumor is multiple, it needs to be removed by single quadrantectomy
* Receive breast conserving surgery with negative margins
* Axillary lymph nodes treatment: Sentinel lymph node biopsy or level I/II axillary lymph node dissection. If the sentinel lymph node is negative, the axillary lymph node dissection can be omitted. If it is positive, level I/II axillary lymph node dissection with or more than 10 lymph nodes is needed.
* The tumor bed is labeled with clips and it can be drawn on the treatment planning system.
* Pathologically confirmed invasive breast cancer
* Pathologically stage is T1-3N0-3M0
* Immunohistochemical examination is conducted to determine the status of ER, PR, HER2, Ki67 after surgery
* No distant metastases
* No supraclavicular or internal mammary nodes metastases
* No neoadjuvant chemotherapy
* Fit for postoperative radiotherapy. No contraindications to radiotherapy
* KPS≥80
* Signed informed consent

Exclusion Criteria:

* T4 or M1 breast cancer
* Supraclavicular or internal mammary nodes metastases
* Pathologically confirmed DCIS only without an invasive component
* Bilateral breast cancer or historically confirmed contralateral invasive breast cancer
* Treated with neoadjuvant chemotherapy or neoadjuvant endocrine therapy
* Multiple lesions can not be removed by single quadrantectomy
* Suspicious unresected and microcalcification, densities, or palpable abnormalities (in the ipsilateral or contralateral breast)
* KPS ≤ 70
* Patients with severe non-malignant comorbidity in cardiovascular or respiration system
* Concurrent or previous malignancy excluding basal or squamous cell carcinoma of the skin
* Previous radiotherapy to the chest wall or regional lymph node areas
* Patients with medical contraindication for radiotherapy: systemic lupus erythematosus, cirrhosis
* Pregnant or lactating
* Conditions indicating that the patient cannot go through the radiation therapy or follow up
* Unable or unwilling to sign informed consent

Primary outcomes:
measure: Loco-regional recurrence (LRR)
timeFrame: 5 years
Secondary outcomes:
measure: Distant metastasis free survival (DMFS)
timeFrame: every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years
measure: Disease free survival (DFS)
timeFrame: every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years
measure: Overall survival (OS)
timeFrame: every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years
measure: Number of patients with radiation-induced acute toxicity assesses by CTCAE4.03
timeFrame: before treatment, after 8 fractions (HF-RTgroup) and 15 fractions (CF-RT and HF-RT groups) and 30 fractions（CF-RT group) irradiation, 2 weeks and 3 months after the irradiation finished
measure: Number of patients with radiation-induced late toxicity assesses by CTCAE4.03
timeFrame: before treatment, every year after the last fraction received through 10 years
measure: Number of patients with radiation-induced late toxicity assesses by LENT-SOMA Toxicity Assessment
timeFrame: before treatment, every year after the last fraction received through 10 years
measure: Harvard/NSABP/RTOG Breast Cosmesis Grades of patients
timeFrame: before treatment, every year after the last fraction received through 10 years
measure: Quality of Life Score assessed by EORTC-QLQ-C30 (version 3)
timeFrame: before treatment, after 15 fractions (HF-RTgroup) or 30 fractions (CF-RT group) irradiation，every year after the treatment finished through 10 years
measure: Quality of Life Score assessed by EORTC breast-cancer module (BR23)
timeFrame: before treatment, after 15 fractions (HF-RTgroup) or 30 fractions (CF-RT group) irradiation, every year after the last fraction received through 10 years
measure: Number and percentage of peripheral blood lymphocytes
timeFrame: before treatment, after 8 fractions (HF-RTgroup) and 15 fractions (CF-RT and HF-RT groups) and 30 fractions（CF-RT group) irradiation
Other outcomes:
Locations:
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Suzhou
country: China
facility: Suzhou Municipal hospital
state: Jiangsu
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
state: Liaoning
city: Shanghai
country: China
facility: Shanghai Huangpu District Central Hospital
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xiaoli Yu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: