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

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.

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.

Interventions

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

Primary outcome measures

• disease free survival (DFS): [Time frame: 6 to 10 years]

Secondary outcome measures (12)

• local recurrence rate [in affected breast] (LR) [Time frame: 6 to 10 years]
• locoregional recurrence rate (LRR) [Time frame: 6 to 10 years]
• disease metastases free survival (DMFS) [Time frame: 6 to 10 years]
• overall survival (OS) [Time frame: 6 to 10 years]
• disease specific survival (DSS) [Time frame: 6 to 10 years]
• Assesment of cosmetic results by the physicians and the patient using a 5 point Scoring System* [Time frame: 6 to 10 years]
• Assesment of cosmetic results by the physicians using breast retraction assessment-Score (BRA Score)* [Time frame: 6 to 10 years]
• Measurement of the quality of life (QOL): functional scale [Time frame: 6 to 10 years]
• Measurement of the quality of life (QOL): symptom-related scale [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 [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 [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. [Time frame: 6 to 10 years]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 16 centers

• St. Marien-Krankenhaus Ahaus — Ahaus
• Hochtaunus-Kliniken — Bad Homburg
• Sana Klinikum Lichtenberg — Berlin
• St. Agnes-Hospital — Bocholt
• Städtisches Klinikum Dessau — Dessau
• Universitätsfrauenklinik UK OWL, Klinikum Lippe — Detmold
• Universitätsklinikum Düsseldorf — Düsseldorf
• Niels-Stensen-Kliniken Franziskus-Hospital Harderberg — Georgsmarienhütte
• … and 8 more centers

Identifiers

NCT: NCT04261244 · NeoRad Breast Cancer Study

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗