NeoRad Breast Cancer Study

Neoadjuvant Chemotherapy Followed by Preoperative Radiotherapy in High-risk Breast Cancer: a Prospective, International Randomised Multicentre-phase III Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: preoperative radiotherapy; Radiation: postoperative radiotherapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1826
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Christiane Matuschek, MD; Phone Number: +492118117994 +492118117994; Email: matuschek@med.uni-duesseldorf.de
• Study Contact Backup: Name: Wilfried Budach, MD; Phone Number: +492118117994 +492118117991; Email: wilfried.budach@med.uni-duesseldorf.de

Study Locations

• Germany
  • Duesseldorf, Germany, 40225
    • Heinrich Heine University Hospital Duesseldorf
    • Contact: Christiane Matuschek, MD; Phone Number: +492118117994; Email: matuschek@med.uni-duesseldorf.de
    • Contact: Wilfried Budach, MD; Phone Number: +492118117991; Email: wilfried.budach@med.uni-duesseldorf.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; preoperative radiotherapy in breast cancer after neoadjuvant chemotherapy	Radiation: preoperative radiotherapy; preoperative radiotherapy instead of postoperative radiotherapy in breast cancer after neoadjuvant chemotherapy
Active Comparator: Standard treatment; standard treatment (postoperative radiotherapy) in breast cancer after neoadjuvant chemotherapy	Radiation: postoperative radiotherapy; postoperative radiotherapy in breast cancer after neoadjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 to 10 years
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.	6 to 10 years
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.	6 to 10 years
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.	6 to 10 years
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.	6 to 10 years
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	6 to 10 years
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.	6 to 10 years
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.	6 to 10 years
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)	6 to 10 years
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	6 to 10 years
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	6 to 10 years
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)	6 to 10 years

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Investigators: Principal Investigator: Christiane Matuschek, MD, University Hosptial Duesseldorf, Department of Radiotherapy and Radiooncology

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): June 30, 2030
• Study Completion (Anticipated): December 31, 2030

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: February 6, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: neoadjuvant chemotherapy; capsular contraction; preoperative radiotherapy; immediate reconstruction
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NeoRadUKD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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