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出境医 / 临床实验 / Hypofractionated Vs Conventional Fractionated Radiotherapy After Breast Conserving Surgery

Hypofractionated Vs Conventional Fractionated Radiotherapy After Breast Conserving Surgery

Study Description
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

Condition or disease Intervention/treatment Phase
Breast Cancer Radiation: Hypofractionated Radiotherapy Radiation: Conventional fractionated Radiotherapy Not Applicable

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.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4052 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast Conserving Surgery:a Multi-center Phase III Randomized Clinical Trial
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2028
Arms and Interventions
Arm Intervention/treatment
Experimental: Hypofractionated Radiotherapy

40 Gy/15 fractions irradiation is delivered to the whole breast, 2.67 Gy per fraction, 5 fractions weekly.

Tumor bed is boosted to 48 Gy simultaneously, 3.2 Gy per fraction, 5 fractions weekly.

Radiation: Hypofractionated Radiotherapy
daily fractions, 2.66 Gy/3.2 Gy per fraction to whole breast/tumor bed, five fractions per week
Other Name: Experimental Arm

Active Comparator: Conventional Irradiation

50 Gy/25 fractions irradiation is delivered to the whole breast, 2 Gy per fraction, 5 fractions weekly.

Additional 10 Gy/5 fractions is boosted to tumor bed sequentially, 2 Gy per fraction, 5 fractions weekly.

Radiation: Conventional fractionated Radiotherapy
daily fractions, 2 Gy per fraction, five fractions per week
Other Name: Standard Arm

Outcome Measures
Primary Outcome Measures :
  1. Loco-regional recurrence (LRR) [ Time Frame: 5 years ]
    Defined as any clinical and biopsy-proven tumor recurrence involving the ipsilateral chest wall and/or regional nodes (including axillary, supraclavicular, infraclavicular, or internal mammary nodes).


Secondary Outcome Measures :
  1. Distant metastasis free survival (DMFS) [ Time Frame: 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 ]
    Distant metastasis is defined as clinical detection of metastatic disease beyond the chest wall and/or regional lymph nodes or death or last visit. Distant metastasis free survival (DMFS) is defined as the interval starting from the date of randomization until to the event.

  2. Disease free survival (DFS) [ Time Frame: 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 ]
    Defined as the interval from the date of randomization to any disease recurrence or death or last visit.

  3. Overall survival (OS) [ Time Frame: 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 ]
    Defined as the interval from the date of randomization to death or last visit.

  4. Number of patients with radiation-induced acute toxicity assesses by CTCAE4.03 [ Time Frame: 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 ]
    Acute toxicity (development of radiation dermatitis, pruritus, pain, radiation esophagitis, and radiation pneumonitis) will be assessed according to toxicity criteria of CTCAE version 4.03 before treatment, during treatment (after 8 fractions irradiation for HF-RTgroup and 15 fractions for CF-RT group) and the end of treatment (15 fractions irradiation for HF-RTgroup and 30 fractions for CF-RT group), 2 weeks and 3 months after the last fraction received.

  5. Number of patients with radiation-induced late toxicity assesses by CTCAE4.03 [ Time Frame: before treatment, every year after the last fraction received through 10 years ]
    Late toxicity (change of skin in irradiated area,impaired shoulder movement ,impaired shoulder movement, brachial plexopathy,ischemic heart disease) will be assessed according to toxicity criteria of CTCAE version 4.03

  6. Number of patients with radiation-induced late toxicity assesses by LENT-SOMA Toxicity Assessment [ Time Frame: before treatment, every year after the last fraction received through 10 years ]
    Development of dyspigmentation, telangiectasia in irradiated area and radiation pulmonary fibrosis will be assessed according to toxicity criteria of LENT-SOMA

  7. Harvard/NSABP/RTOG Breast Cosmesis Grades of patients [ Time Frame: before treatment, every year after the last fraction received through 10 years ]
    The cosmetic outcomes will be evaluated by radiation oncologists, nurses and patients using digital photographs and Harvard/NSABP/RTOG Breast Cosmesis Grading Scale. Harvard/NSABP/RTOG Breast Cosmesis Grading Scale classifies the overall aesthetic results in four categories from excellent, good, fair to poor.

  8. Quality of Life Score assessed by EORTC-QLQ-C30 (version 3) [ Time Frame: before treatment, after 15 fractions (HF-RTgroup) or 30 fractions (CF-RT group) irradiation,every year after the treatment finished through 10 years ]
    Patients' quality of life will be assessed using self-administered questionnaire EORTC-QLQ-C30 (version 3)

  9. Quality of Life Score assessed by EORTC breast-cancer module (BR23) [ Time Frame: before treatment, after 15 fractions (HF-RTgroup) or 30 fractions (CF-RT group) irradiation, every year after the last fraction received through 10 years ]
    Patients' quality of life will be assessed using self-administered questionnaire EORTC breast-cancer module (BR23)

  10. Number and percentage of peripheral blood lymphocytes [ Time Frame: before treatment, after 8 fractions (HF-RTgroup) and 15 fractions (CF-RT and HF-RT groups) and 30 fractions(CF-RT group) irradiation ]
    peripheral blood lymphocytes will be assessed before, during treatment (after 8 fractions irradiation for HF-RTgroup and 15 fractions for CF-RT group) and the end of treatment (15 fractions irradiation for HF-RTgroup and 30 fractions for CF-RT group). The number and percentage of peripheral blood lymphocytes will be assessed the correlation with the grade of acute toxicity assessed by CTCAE 4.03


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Xiaoli Yu, MD, PhD +86-13817893133 stephanieyxl@hotmail.com
Contact: Jurui Luo, PhD +86-13162996951 juruiluo@hotmail.com

Locations
Layout table for location information
China, Guizhou
Guizhou Provincial People's Hospital Not yet recruiting
Guiyang, Guizhou, China, 550002
Contact: Xin Li, PhD    13984157730    315332722@qq.com   
China, Jiangsu
Suzhou Municipal hospital Recruiting
Suzhou, Jiangsu, China, 215000
Contact: Qunchao Hu, PhD    +86-17712679728    hqc82@163.com   
China, Liaoning
The Second Hospital of Dalian Medical University Not yet recruiting
Dalian, Liaoning, China, 116044
Contact: Yanqin Yang, PhD    17709870293    yqtoday2008@126.com   
China, Shanghai
Shanghai Huangpu District Central Hospital Recruiting
Shanghai, Shanghai, China, 200002
Contact: Gang Chen    021-63212487    fodeng73@163.com   
Fudan University Shanghai Cancer Center Recruiting
Shanghai, Shanghai, China, 200032
Contact: Xiaoli Yu, MD,PhD    +86-13817893133    stephanieyxl@hotmail.com   
Contact: Jurui Luo, PhD    +86-13162996951    juruiluo@hotmail.com   
Sponsors and Collaborators
Fudan University
Investigators
Layout table for investigator information
Principal Investigator: Xiaoli Yu, MD, PhD Fudan University
Tracking Information
First Submitted Date  ICMJE July 6, 2019
First Posted Date  ICMJE July 18, 2019
Last Update Posted Date July 18, 2019
Actual Study Start Date  ICMJE July 1, 2018
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
Loco-regional recurrence (LRR) [ Time Frame: 5 years ]
Defined as any clinical and biopsy-proven tumor recurrence involving the ipsilateral chest wall and/or regional nodes (including axillary, supraclavicular, infraclavicular, or internal mammary nodes).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
  • Distant metastasis free survival (DMFS) [ Time Frame: 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 ]
    Distant metastasis is defined as clinical detection of metastatic disease beyond the chest wall and/or regional lymph nodes or death or last visit. Distant metastasis free survival (DMFS) is defined as the interval starting from the date of randomization until to the event.
  • Disease free survival (DFS) [ Time Frame: 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 ]
    Defined as the interval from the date of randomization to any disease recurrence or death or last visit.
  • Overall survival (OS) [ Time Frame: 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 ]
    Defined as the interval from the date of randomization to death or last visit.
  • Number of patients with radiation-induced acute toxicity assesses by CTCAE4.03 [ Time Frame: 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 ]
    Acute toxicity (development of radiation dermatitis, pruritus, pain, radiation esophagitis, and radiation pneumonitis) will be assessed according to toxicity criteria of CTCAE version 4.03 before treatment, during treatment (after 8 fractions irradiation for HF-RTgroup and 15 fractions for CF-RT group) and the end of treatment (15 fractions irradiation for HF-RTgroup and 30 fractions for CF-RT group), 2 weeks and 3 months after the last fraction received.
  • Number of patients with radiation-induced late toxicity assesses by CTCAE4.03 [ Time Frame: before treatment, every year after the last fraction received through 10 years ]
    Late toxicity (change of skin in irradiated area,impaired shoulder movement ,impaired shoulder movement, brachial plexopathy,ischemic heart disease) will be assessed according to toxicity criteria of CTCAE version 4.03
  • Number of patients with radiation-induced late toxicity assesses by LENT-SOMA Toxicity Assessment [ Time Frame: before treatment, every year after the last fraction received through 10 years ]
    Development of dyspigmentation, telangiectasia in irradiated area and radiation pulmonary fibrosis will be assessed according to toxicity criteria of LENT-SOMA
  • Harvard/NSABP/RTOG Breast Cosmesis Grades of patients [ Time Frame: before treatment, every year after the last fraction received through 10 years ]
    The cosmetic outcomes will be evaluated by radiation oncologists, nurses and patients using digital photographs and Harvard/NSABP/RTOG Breast Cosmesis Grading Scale. Harvard/NSABP/RTOG Breast Cosmesis Grading Scale classifies the overall aesthetic results in four categories from excellent, good, fair to poor.
  • Quality of Life Score assessed by EORTC-QLQ-C30 (version 3) [ Time Frame: before treatment, after 15 fractions (HF-RTgroup) or 30 fractions (CF-RT group) irradiation,every year after the treatment finished through 10 years ]
    Patients' quality of life will be assessed using self-administered questionnaire EORTC-QLQ-C30 (version 3)
  • Quality of Life Score assessed by EORTC breast-cancer module (BR23) [ Time Frame: before treatment, after 15 fractions (HF-RTgroup) or 30 fractions (CF-RT group) irradiation, every year after the last fraction received through 10 years ]
    Patients' quality of life will be assessed using self-administered questionnaire EORTC breast-cancer module (BR23)
  • Number and percentage of peripheral blood lymphocytes [ Time Frame: before treatment, after 8 fractions (HF-RTgroup) and 15 fractions (CF-RT and HF-RT groups) and 30 fractions(CF-RT group) irradiation ]
    peripheral blood lymphocytes will be assessed before, during treatment (after 8 fractions irradiation for HF-RTgroup and 15 fractions for CF-RT group) and the end of treatment (15 fractions irradiation for HF-RTgroup and 30 fractions for CF-RT group). The number and percentage of peripheral blood lymphocytes will be assessed the correlation with the grade of acute toxicity assessed by CTCAE 4.03
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hypofractionated Vs Conventional Fractionated Radiotherapy After Breast Conserving Surgery
Official Title  ICMJE Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast Conserving Surgery:a Multi-center Phase III Randomized Clinical Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Radiation: Hypofractionated Radiotherapy
    daily fractions, 2.66 Gy/3.2 Gy per fraction to whole breast/tumor bed, five fractions per week
    Other Name: Experimental Arm
  • Radiation: Conventional fractionated Radiotherapy
    daily fractions, 2 Gy per fraction, five fractions per week
    Other Name: Standard Arm
Study Arms  ICMJE
  • Experimental: Hypofractionated Radiotherapy

    40 Gy/15 fractions irradiation is delivered to the whole breast, 2.67 Gy per fraction, 5 fractions weekly.

    Tumor bed is boosted to 48 Gy simultaneously, 3.2 Gy per fraction, 5 fractions weekly.

    Intervention: Radiation: Hypofractionated Radiotherapy
  • Active Comparator: Conventional Irradiation

    50 Gy/25 fractions irradiation is delivered to the whole breast, 2 Gy per fraction, 5 fractions weekly.

    Additional 10 Gy/5 fractions is boosted to tumor bed sequentially, 2 Gy per fraction, 5 fractions weekly.

    Intervention: Radiation: Conventional fractionated Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 17, 2019)
4052
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2028
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xiaoli Yu, MD, PhD +86-13817893133 stephanieyxl@hotmail.com
Contact: Jurui Luo, PhD +86-13162996951 juruiluo@hotmail.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04025164
Other Study ID Numbers  ICMJE FDRT-BC007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Xiaoli Yu, Fudan University
Study Sponsor  ICMJE Fudan University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Xiaoli Yu, MD, PhD Fudan University
PRS Account Fudan University
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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