Clinical trial NCT04261244: NeoRad Breast Cancer Study
Official title: Preoperative Radiotherapy Versus Postoperative Radiotherapy After Neoadjuvant Chemotherapy ("NeoRad") in High-risk Breast Cancer: a Prospektiv, Randomized, International Multicenter Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: neoadjuvant chemotherapy
preoperative radiotherapy
capsular contraction
immediate reconstruction
Lead sponsor: Bielefeld University
Sponsor class: OTHER
First posted: 2020-02-07
Enrollment: 1826
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, multicenter
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: disease free survival (DFS):
timeFrame: 6 to 10 years
Secondary outcomes:
measure: local recurrence rate [in affected breast] (LR)
timeFrame: 6 to 10 years
measure: locoregional recurrence rate (LRR)
timeFrame: 6 to 10 years
measure: disease metastases free survival (DMFS)
timeFrame: 6 to 10 years
measure: overall survival (OS)
timeFrame: 6 to 10 years
measure: disease specific survival (DSS)
timeFrame: 6 to 10 years
measure: Assesment of cosmetic results by the physicians and the patient using a 5 point Scoring System*
timeFrame: 6 to 10 years
measure: Assesment of cosmetic results by the physicians using breast retraction assessment-Score (BRA Score)*
timeFrame: 6 to 10 years
measure: Measurement of the quality of life (QOL): functional scale
timeFrame: 6 to 10 years
measure: Measurement of the quality of life (QOL): symptom-related scale
timeFrame: 6 to 10 years
measure: Assessment of arm lymphedema rates by the physicians using common toxicity criteria for adverse events CTCAE, version 5.0
timeFrame: 6 to 10 years
measure: 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
timeFrame: 6 to 10 years
measure: Assessment of treatment-related toxicity measured by the physicians using standardized common toxicity criteria for adverse events CTCAE, version 5.0.
timeFrame: 6 to 10 years
Other outcomes:
Locations:
city: Ahaus
country: Germany
facility: St. Marien-Krankenhaus Ahaus
city: Bad Homburg
country: Germany
facility: Hochtaunus-Kliniken
city: Berlin
country: Germany
facility: Sana Klinikum Lichtenberg
city: Bocholt
country: Germany
facility: St. Agnes-Hospital
city: Dessau-Roßlau
country: Germany
facility: Städtisches Klinikum Dessau
city: Detmold
country: Germany
facility: Universitätsfrauenklinik UK OWL, Klinikum Lippe
city: Duesseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Georgsmarienhütte
country: Germany
facility: Niels-Stensen-Kliniken Franziskus-Hospital Harderberg
city: Hameln
country: Germany
facility: Sana Klinikum Hameln-Pyrmont
city: Offenbach am Main
country: Germany
facility: Sana Klinikum Offenbach
city: Ostfildern
country: Germany
facility: medius Klinik Ostfildern-Ruit
city: Schweinfurt
country: Germany
facility: Leopoldina Krankenhaus Schweinfurt
city: Stendal
country: Germany
facility: Johanniter-Krankenhaus Stendal
city: Winnenden
country: Germany
facility: Rems-Murr-Klinikum Winnenden
city: Wuppertal
country: Germany
facility: Helios Universitätsklinikum Wuppertal
city: Zwickau
country: Germany
facility: Heinrich-Braun-Klinikum
Study officials:
affiliation: Bielefeld University
name: Christiane M Prof., MD Prof.
role: STUDY_CHAIR
References: