The goal of the study is to assess the safety and effectiveness of the combination of anti-PD1 immunotherapy (pembrolizumab) and radiotherapy in the preoperative treatment of HER2-negative breast cancer resistant to classical chemotherapy. The subject of the intervention will be: 1. Randomly assigned in a 2:1 ratio and double-blinded addition of pre-operative immunotherapy with pembrolizumab or placebo to standard chemotherapy 2. Addition of preoperative radiotherapy boost delivered with a CyberKnife radiosurgery system concomitantly with the use of paclitaxel (+/- carboplatin) and pembrolizumab / placebo.
The study aims to assess the safety and effectiveness of the combination of anti-PD1 (PD-1, programmed cell death-1) immunotherapy (pembrolizumab) with radiotherapy in the preoperative treatment of triple-negative or luminal HER2-negative (HER2, Human epidermal growth factor receptor 2) (breast cancer, stage IIA/IIB/III/IV (with an acceptable oligometastatic form), resistant to classical chemotherapy After screening and administration of standard induction chemotherapy, the study will be conducted in a group of patients selected on the basis of lack of metabolic response after the 1st cycle of chemotherapy, and the subject of the intervention will be: * addition of preoperative immunotherapy with pembrolizumab or placebo to standard chemotherapy, using a double-blind randomized trial in a ratio of 2:1, respectively * addition of a boost of preoperative robotic stereotactic radiotherapy in all patients, simultaneously with the use of paclitaxel +/- carboplatin and pembrolizumab/placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
78
Preoperative immunotherapy (200 mg, infusion every 21 days, 4 administrations planned)
Boost of preoperative robotic stereotactic radiotherapy
0,9% NaCl in the volume 100 ml
Maria Sklodowska-Curie National Research Institute of Oncology , Gliwice Branch
Gliwice, Poland
RECRUITINGThe histopathological confirmation of complete tumor regression in postoperative material performed in a population of 52 patients receiving immunotherapy in combination with radiotherapy
The statistical analysis will be performed by comparison to the initial assumptions, according to Simon's scheme. The finding of complete tumor regression (confirmed histopathologically) in more than 11 patients out of the group of 52 enrolled will be treated as fulfillment of the primary endpoint.
Time frame: Rating histopathology of the collected material during surgery
Assessment of complete regression in postoperative histopathological examination in the population of all 78 patients receiving preoperative chemotherapy and radiotherapy
The finding of of complete tumor regression in more than 13 patients out of the group of 78 included and receiving both chemotherapy and radiotherapy will be treated as fulfillment of the secondary endpoint criterion.
Time frame: Rating histopathology of the collected material during surgery
The assessment of the response to preoperative treatment by assessing postoperative material in histopathological examination
Assessment of regression under the influence of pembrolizumab in postoperative histopathological examination using the quantitative method, taking into account the degree of partial regression
Time frame: Rating histopathology of the collected material during surgery
The comparison of the Invasive Disease Free Survival time the group treated with pembrolizumab with radiotherapy to the group treated with placebo with radiotherapy
Invasive Disease Free Survival time will be evaluated according to Proposal for Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials
Time frame: The entire observation period,an average of 4 years
Quality of life evaluated by QLQ-C30 questionnaire (Quality of Live questionnaire) comparision beteewen groups
General health condition based on the QLQ-C30 scale
Time frame: Assessment approximately 4 months after surgical treatment
Safety and tolerance (number of participants with treatment-related adverse events).
Assessment of safety and tolerance of treatment according to Common Terminology Criteria for Adverse Events v. 5.0;
Time frame: During the study, an average of 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.