NeoRad Breast Cancer Study

Phase 3RecruitingNCT04261244

Bielefeld University1,826 enrolled

Overview

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.

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. The Study Chairman of the NEORAD trial is Prof. Dr. med. Christiane Matuschek. The deputies of the Study Chairman are Prof. Dr. med. Wilfried Budach and Prof. Dr. med. Tanja Fehm.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,826

Conditions

Breast Cancer

Interventions

preoperative radiotherapyRADIATION

preoperative radiotherapy instead of postoperative radiotherapy in breast cancer after neoadjuvant chemotherapy

postoperative radiotherapyRADIATION

postoperative radiotherapy in breast cancer after neoadjuvant chemotherapy

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically proven invasive, unilateral breast cancer * Indication for radiotherapy * Indication for neoadjuvant chemotherapy (+/- antibody treatment or other targeted therapies) in accordance with national and international guidelines * Female * Informed consent for the trial signed by the patient * Hormone receptor and HER2 status: no restrictions * All grades G1-G3 * Age ≥ 18 years at the time of informed consent * Performance status ≤ 2 * No pre-existing conditions that prohibit therapy Exclusion Criteria: * Neoadjuvant treatment solely with endocrine therapy * Bilateral breast cancer * Pregnancy or lactation * Prior radiotherapy of the thorax * 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 edema ≥°II of the arm at the side of the breast cancer * Other medical conditions that prohibit the neoadjuvant radiotherapy (i.e. Expected non-compliance, etc.) * Male patients * Patients who have previously been assessed for chemotherapy response

Locations (16)

St. Marien-Krankenhaus Ahaus

Ahaus, Germany

RECRUITING

Hochtaunus-Kliniken

Bad Homburg, Germany

Outcomes

Primary Outcomes

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.

Time frame: 6 to 10 years

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 6 to 10 years

Central Contacts

Christiane Matuschek, MD Prof.

CONTACT

+495215812901 christiane.matuschek@uni-bielefeld.de

Deborah Wöstenfeld, M. A.

CONTACT

+495215812972 deborah.woestenfeld@uni-bielefeld.de

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Sana Klinikum Lichtenberg

Berlin, Germany

RECRUITING

St. Agnes-Hospital

Bocholt, Germany

RECRUITING

Städtisches Klinikum Dessau

Dessau, Germany

RECRUITING

Universitätsfrauenklinik UK OWL, Klinikum Lippe

Detmold, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

RECRUITING

Niels-Stensen-Kliniken Franziskus-Hospital Harderberg

Georgsmarienhütte, Germany

RECRUITING

Sana Klinikum Hameln-Pyrmont

Hamelin, Germany

RECRUITING

Sana Klinikum Offenbach

Offenbach, Germany

RECRUITING

...and 6 more locations

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

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 6 to 10 years