Back to resultsNeoRad Breast Cancer Study
Primary Purpose
Breast Cancer
Status
Not yet recruiting
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
preoperative radiotherapy
postoperative radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring neoadjuvant chemotherapy, preoperative radiotherapy, capsular contraction, immediate reconstruction
Eligibility Criteria
Inclusion Criteria:
- Pathological evidence of breast cancer
- Indication for neoadjuvant chemotherapy in accordance with national and international guidelines
- Informed consent for NACT signed by the patient
- T2-T4 (non-inflammatory)
- T1, if G3,* triple negative, Her2 positive, or cN+/pN+
- Hormone receptor and HER2/neu status: no restrictions
- All grades G1-G3
- Age ≥18 years at the time of randomisation
- Performance status ≤ 2
- No pre-existing conditions that prohibit therapy
- Signed consent form regarding registration, randomisation, collecting, and saving of personal data
Exclusion Criteria:
- Pregnancy or lactation
- Prior radiotherapy of the affected or contralateral breast
- Inflammatory breast cancer
- Connective tissue disease, including rheumatoid arthritis and thromboangiitis obliterans
- Pre-existing symptomatic chronic lung disease (fibrosis, pneumoconiosis, adult-onset allergies, such as farmer's lung, severe lung emphysema, COPD °III)
- Cardiac comorbidities: symptomatic coronary heart disease, prior heart attack, heart failure NYHA II or AHA C, pacemaker, and/or implanted defibrillator
- Malignoma except basalioma or in-situ-carcinomas in complete response
- Distant metastasis
- Plexopathies of the arm of the treated side
- Stiffness of the shoulder of the arm of the side of the breast cancer of any origin (e.g. following a road accident)
- Lymph oedema °II of the arm at the side of the breast cancer
- Missing signature on consent form
- Other medical conditions that prohibit the neoadjuvant chemotherapy (i.e. HIV, psychiatric diseases, non-compliance, etc.)
Sites / Locations
- Heinrich Heine University Hospital Duesseldorf
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Experimental Arm
Standard treatment
Arm Description
preoperative radiotherapy in breast cancer after neoadjuvant chemotherapy
standard treatment (postoperative radiotherapy) in breast cancer after neoadjuvant chemotherapy
Outcomes
Primary Outcome Measures
disease free survival (DFS):
Time interval in which the patient does not show any signs or symptoms of the treated cancer (local or regional recurrence, distant metastases, or death of any cause) beginning after randomisation to a study arm.
This is a way to measure how well the new treatment is working.
Secondary Outcome Measures
local recurrence rate [in affected breast] (LR)
Rate of cancer that has recurred at the same location as the primary cancer. This is a way to measure how well the new treatment is working.
locoregional recurrence rate (LRR)
Rate of new cancer at any locations (regional lymph nodes, chest wall/mastectomy site) on side which was previously affected by the primary cancer.
This is a way to measure how well the new treatment is working.
disease metastases free survival (DMFS)
Time interval beginning after randomisation in which the patient survives and the cancer has not metastasized.
This is a way to measure how well the new treatment is working.
overall survival (OS)
Length of time beginning after randomisation in the study that the patient survives.
This is a way to measure how well the new treatment is working.
disease specific survival (DSS)
Length of time from the beginning of the study after randomisation in a study arm that the patient survives the specific cancer.
This is a way to measure how well the new treatment is working.
Assesment of cosmetic results by the physicians and the patient using a 5 point Scoring System*
A grading scale is provided for cosmetic results (5 Point Scoring System):
E0 Excellent aesthetic result: At first sight no visible therapy sequellae. Both breasts have a similar appearance E1 Good: minimal changes in pigmentation, a visible scar, localized teleangieectasia.
E2 Moderate: marked sequellae with a clear deformation of the breast contour, nipple displacement, or marked skin changes, but yet "acceptable".
E3 Bad: severe retraction or fibrosis, severe teleangiectasia. E4 Complications: skin necrosis
Assesment of cosmetic results by the physicians using breast retraction assessment-Score (BRA Score)*
*The BRA Score measures breast symmetry of the treated breast in comparison to the untreated breast. The average in the general population is 1.2 cm. A higher BRA score is worse. A BRA score of 0 cm is optimal.
Measurement of the quality of life (QOL): functional scale
QoL will be assessed by EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 questionnaires for overall QoL and EORTC QLQ-BR23 for breast-specific QoL. The QLQ-C30 consists of 30 questions categorized in functional and symptom-specific scales and provides a global score through two general questions concerning health and quality of life. QLQ-BR23 is a standard instrument for measuring QoL in patients with breast cancer. The questionnaire has 23 items with four possible answers each (not at all, a little, quite a bit, very much). Results are reported using functional scales (e.g. body image, sexual functioning) and symptom-related items (e.g. systemic therapy side effects, breast symptoms). It is also common practice to classify the summary scores into four distinct categories with functional scales (0-25 bad; 26-50 moderate; 51-75 good; 76-100 excellent) and symptom-related scales.
Measurement of the quality of life (QOL): symptom-related scale
QoL will be assessed by EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 questionnaires for overall QoL and EORTC QLQ-BR23 for breast-specific QoL. The QLQ-C30 consists of 30 questions categorized in functional and symptom-specific scales and provides a global score through two general questions concerning health and quality of life. QLQ-BR23 is a standard instrument for measuring QoL in patients with breast cancer. The questionnaire has 23 items with four possible answers each (not at all, a little, quite a bit, very much). Results are reported using functional scales (e.g. body image, sexual functioning) and symptom-related items (e.g. systemic therapy side effects, breast symptoms). It is also common practice to classify the summary scores into four distinct categories with functional scales and symptom-related scales: (0-25 excellent; 26-50 good; 51-75 moderate, 76-100 bad)
Assessment of arm lymphedema rates by the physicians using common toxicity criteria for adverse events CTCAE, version 5.0
Lymphedema: 'A disorder characterized by excessive fluid collection in tissues that causes swelling.'
A grading scale is provided for arm lymphoedema rates higher than Grade 1 of the irradiated side (0= "not present", 1= "Trace thickening or faint discoloration", 2= "Marked discoloration; leathery skin texture; papillary formation; limiting instrumental ADL*", 3= "Severe symptoms; limiting self care ADL") using common toxicity criteria for adverse events CTCAE, version 5.0
*ADL = activities of daily living
Assessment of plexopathia higher than Grade 1 of brachial plexus on irradiated side by the physicians using common toxicity criteria for adverse events CTCAE, version 5.0
Brachial plexopathia:'"A disorder characterized by regional paresthesia of the brachial plexus, marked discomfort and muscle weakness, and limited movement in the arm or hand.'
A grading scale is provided for plexopathia of brachial plexus on the irradiated side higher than Grade 1 (0= "not present", 1= "Aysmptomatic; clinical or diagnostic observations only; intervention not indicated", 2= "Moderate symptoms; limiting instrumental ADL*", 3= "Severe symptoms, limiting self care ADL") using common toxicity criteria for adverse events CTCAE, version 5.0
*ADL = activities of daily living
Assessment of treatment-related toxicity measured by the physicians using standardized common toxicity criteria for adverse events CTCAE, version 5.0.
A grading scale is provided for each side effect (0= not present, 1=asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, 3=moderate; minimal, local or noninvasive intervention indicated; -4=severe or medically significant but not immediately life-threatening)
Full Information
NCT ID
NCT04261244
First Posted
September 30, 2019
Last Updated
February 13, 2020
Sponsor
Heinrich-Heine University, Duesseldorf
1. Study Identification
Unique Protocol Identification Number
NCT04261244
Brief Title
NeoRad Breast Cancer Study
Official Title
Neoadjuvant Chemotherapy Followed by Preoperative Radiotherapy in High-risk Breast Cancer: a Prospective, International Randomised Multicentre-phase III Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2020 (Anticipated)
Primary Completion Date
June 30, 2030 (Anticipated)
Study Completion Date
December 31, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Heinrich-Heine University, Duesseldorf
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The NEORAD trial tests whether preoperative radiotherapy results in an improved DFS and less radiation induced late effect compared to postoperative radiotherapy in higher risk breast cancer after NACT.
Detailed Description
The standard of care for high-risk breast cancer consists of neoadjuvant chemotherapy and surgery followed by postoperative whole breast/chest wall irradiation+/- an additional boost (= irradiation restricted to the tumour bed in the case of breast-conserving therapy). In case of lymph node involvement in most patients require additional radiation of the regional lymph nodes. Adjuvant radiotherapy significantly reduces ipsilateral breast cancer recurrences, breast cancer specific mortality, and overall mortality. The optimal time of radiotherapy in patients, who are candidates for neoadjuvant chemotherapy (NACT) has never been addressed in a randomised controlled trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
neoadjuvant chemotherapy, preoperative radiotherapy, capsular contraction, immediate reconstruction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
randomized, multicenter
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1826 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental Arm
Arm Type
Experimental
Arm Description
preoperative radiotherapy in breast cancer after neoadjuvant chemotherapy
Arm Title
Standard treatment
Arm Type
Active Comparator
Arm Description
standard treatment (postoperative radiotherapy) in breast cancer after neoadjuvant chemotherapy
Intervention Type
Radiation
Intervention Name(s)
preoperative radiotherapy
Intervention Description
preoperative radiotherapy instead of postoperative radiotherapy in breast cancer after neoadjuvant chemotherapy
Intervention Type
Radiation
Intervention Name(s)
postoperative radiotherapy
Intervention Description
postoperative radiotherapy in breast cancer after neoadjuvant chemotherapy
Primary Outcome Measure Information:
Title
disease free survival (DFS):
Description
Time interval in which the patient does not show any signs or symptoms of the treated cancer (local or regional recurrence, distant metastases, or death of any cause) beginning after randomisation to a study arm.
This is a way to measure how well the new treatment is working.
Time Frame
6 to 10 years
Secondary Outcome Measure Information:
Title
local recurrence rate [in affected breast] (LR)
Description
Rate of cancer that has recurred at the same location as the primary cancer. This is a way to measure how well the new treatment is working.
Time Frame
6 to 10 years
Title
locoregional recurrence rate (LRR)
Description
Rate of new cancer at any locations (regional lymph nodes, chest wall/mastectomy site) on side which was previously affected by the primary cancer.
This is a way to measure how well the new treatment is working.
Time Frame
6 to 10 years
Title
disease metastases free survival (DMFS)
Description
Time interval beginning after randomisation in which the patient survives and the cancer has not metastasized.
This is a way to measure how well the new treatment is working.
Time Frame
6 to 10 years
Title
overall survival (OS)
Description
Length of time beginning after randomisation in the study that the patient survives.
This is a way to measure how well the new treatment is working.
Time Frame
6 to 10 years
Title
disease specific survival (DSS)
Description
Length of time from the beginning of the study after randomisation in a study arm that the patient survives the specific cancer.
This is a way to measure how well the new treatment is working.
Time Frame
6 to 10 years
Title
Assesment of cosmetic results by the physicians and the patient using a 5 point Scoring System*
Description
A grading scale is provided for cosmetic results (5 Point Scoring System):
E0 Excellent aesthetic result: At first sight no visible therapy sequellae. Both breasts have a similar appearance E1 Good: minimal changes in pigmentation, a visible scar, localized teleangieectasia.
E2 Moderate: marked sequellae with a clear deformation of the breast contour, nipple displacement, or marked skin changes, but yet "acceptable".
E3 Bad: severe retraction or fibrosis, severe teleangiectasia. E4 Complications: skin necrosis
Time Frame
6 to 10 years
Title
Assesment of cosmetic results by the physicians using breast retraction assessment-Score (BRA Score)*
Description
*The BRA Score measures breast symmetry of the treated breast in comparison to the untreated breast. The average in the general population is 1.2 cm. A higher BRA score is worse. A BRA score of 0 cm is optimal.
Time Frame
6 to 10 years
Title
Measurement of the quality of life (QOL): functional scale
Description
QoL will be assessed by EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 questionnaires for overall QoL and EORTC QLQ-BR23 for breast-specific QoL. The QLQ-C30 consists of 30 questions categorized in functional and symptom-specific scales and provides a global score through two general questions concerning health and quality of life. QLQ-BR23 is a standard instrument for measuring QoL in patients with breast cancer. The questionnaire has 23 items with four possible answers each (not at all, a little, quite a bit, very much). Results are reported using functional scales (e.g. body image, sexual functioning) and symptom-related items (e.g. systemic therapy side effects, breast symptoms). It is also common practice to classify the summary scores into four distinct categories with functional scales (0-25 bad; 26-50 moderate; 51-75 good; 76-100 excellent) and symptom-related scales.
Time Frame
6 to 10 years
Title
Measurement of the quality of life (QOL): symptom-related scale
Description
QoL will be assessed by EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 questionnaires for overall QoL and EORTC QLQ-BR23 for breast-specific QoL. The QLQ-C30 consists of 30 questions categorized in functional and symptom-specific scales and provides a global score through two general questions concerning health and quality of life. QLQ-BR23 is a standard instrument for measuring QoL in patients with breast cancer. The questionnaire has 23 items with four possible answers each (not at all, a little, quite a bit, very much). Results are reported using functional scales (e.g. body image, sexual functioning) and symptom-related items (e.g. systemic therapy side effects, breast symptoms). It is also common practice to classify the summary scores into four distinct categories with functional scales and symptom-related scales: (0-25 excellent; 26-50 good; 51-75 moderate, 76-100 bad)
Time Frame
6 to 10 years
Title
Assessment of arm lymphedema rates by the physicians using common toxicity criteria for adverse events CTCAE, version 5.0
Description
Lymphedema: 'A disorder characterized by excessive fluid collection in tissues that causes swelling.'
A grading scale is provided for arm lymphoedema rates higher than Grade 1 of the irradiated side (0= "not present", 1= "Trace thickening or faint discoloration", 2= "Marked discoloration; leathery skin texture; papillary formation; limiting instrumental ADL*", 3= "Severe symptoms; limiting self care ADL") using common toxicity criteria for adverse events CTCAE, version 5.0
*ADL = activities of daily living
Time Frame
6 to 10 years
Title
Assessment of plexopathia higher than Grade 1 of brachial plexus on irradiated side by the physicians using common toxicity criteria for adverse events CTCAE, version 5.0
Description
Brachial plexopathia:'"A disorder characterized by regional paresthesia of the brachial plexus, marked discomfort and muscle weakness, and limited movement in the arm or hand.'
A grading scale is provided for plexopathia of brachial plexus on the irradiated side higher than Grade 1 (0= "not present", 1= "Aysmptomatic; clinical or diagnostic observations only; intervention not indicated", 2= "Moderate symptoms; limiting instrumental ADL*", 3= "Severe symptoms, limiting self care ADL") using common toxicity criteria for adverse events CTCAE, version 5.0
*ADL = activities of daily living
Time Frame
6 to 10 years
Title
Assessment of treatment-related toxicity measured by the physicians using standardized common toxicity criteria for adverse events CTCAE, version 5.0.
Description
A grading scale is provided for each side effect (0= not present, 1=asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, 3=moderate; minimal, local or noninvasive intervention indicated; -4=severe or medically significant but not immediately life-threatening)
Time Frame
6 to 10 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathological evidence of breast cancer
Indication for neoadjuvant chemotherapy in accordance with national and international guidelines
Informed consent for NACT signed by the patient
T2-T4 (non-inflammatory)
T1, if G3,* triple negative, Her2 positive, or cN+/pN+
Hormone receptor and HER2/neu status: no restrictions
All grades G1-G3
Age ≥18 years at the time of randomisation
Performance status ≤ 2
No pre-existing conditions that prohibit therapy
Signed consent form regarding registration, randomisation, collecting, and saving of personal data
Exclusion Criteria:
Pregnancy or lactation
Prior radiotherapy of the affected or contralateral breast
Inflammatory breast cancer
Connective tissue disease, including rheumatoid arthritis and thromboangiitis obliterans
Pre-existing symptomatic chronic lung disease (fibrosis, pneumoconiosis, adult-onset allergies, such as farmer's lung, severe lung emphysema, COPD °III)
Cardiac comorbidities: symptomatic coronary heart disease, prior heart attack, heart failure NYHA II or AHA C, pacemaker, and/or implanted defibrillator
Malignoma except basalioma or in-situ-carcinomas in complete response
Distant metastasis
Plexopathies of the arm of the treated side
Stiffness of the shoulder of the arm of the side of the breast cancer of any origin (e.g. following a road accident)
Lymph oedema °II of the arm at the side of the breast cancer
Missing signature on consent form
Other medical conditions that prohibit the neoadjuvant chemotherapy (i.e. HIV, psychiatric diseases, non-compliance, etc.)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christiane Matuschek, MD
Phone
+492118117994
Ext
+492118117994
Email
matuschek@med.uni-duesseldorf.de
First Name & Middle Initial & Last Name or Official Title & Degree
Wilfried Budach, MD
Phone
+492118117991
Ext
+492118117994
Email
wilfried.budach@med.uni-duesseldorf.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christiane Matuschek, MD
Organizational Affiliation
University Hosptial Duesseldorf, Department of Radiotherapy and Radiooncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Heinrich Heine University Hospital Duesseldorf
City
Duesseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christiane Matuschek, MD
Phone
+492118117994
Email
matuschek@med.uni-duesseldorf.de
First Name & Middle Initial & Last Name & Degree
Wilfried Budach, MD
Phone
+492118117991
Email
wilfried.budach@med.uni-duesseldorf.de
12. IPD Sharing Statement
Plan to Share IPD
No
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NeoRad Breast Cancer Study
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