The aim of this study is to investigate whether the application of concomitant modulated electro-hyperthermia in a neoadjuvant chemotherapeutic setting is beneficial for patients with HER2-negative, stage II-III breast cancer.
This study is a pivotal, randomized (1:1), open-label, two-treatment group, single-centre trial of Oncotherm EHY-2030, a modulated electro-hyperthermia (mEHT) device. Female patients aged 18 years or older with locally advanced, unilaterally localized HER2-negative breast cancer requiring neoadjuvant treatment are eligible for the study. In the study, the wTAX (+ carboplatin) +AC neoadjuvant chemotherapy protocol will be administered according to the routine daily regimen, with or without mEHT three times a week during the wTAX (+ carboplatin) period. Carboplatin will be administered for patients with triple-negative breast cancer only. Primary objective: to compare whether the percentage of tumor size decrease determined by imaging techniques is different in the two treatment groups? Secondary and other objectives: * Is complete pathological response (pCR) more common in the mEHT-treated group? * Does the pattern of treatment response (pCR : pPR : pNR) differ between the two groups? * Is the quality of life of patients different in the two study groups? * Is there any treatment-related changes in the routine laboratory parameters such as blood count, liver enzymes, renal function? And do these differ in the two study arms? * Safety and tolerability analysis of the device.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
71
Oncotherm EHY-2030 is a non-invasive electromagnetic devices with known anti-tumoral effects. It operates in a precision capacitive coupled impedance matched way, working on a radiofrequency of 13.56 MHz. mEHT exploits various biophysical differences of cancer cells. For example, energy absorption on the membrane rafts is different than those of healthy host cells, and damage-associated molecular patterns (DAMPS) will also occur leading to programmed or immunogenic tumor cell death. mEHT can enhance DNA fragmentation of tumor cells, increase the fraction of cells with low mitochondrial membrane potential, increase the concentration of intracellular Ca2+, increase the Fas, c-Jun N-terminal kinases and MAPK/ERK signaling pathways, increase the expression of pro-apoptotic Bcl-2 family proteins and can up-regulate the expression of genes associated with the molecular function of cell death (EGR1, JUN, and CDKN1A) and silencing others associated with cytoprotective functions.
weekly paclitaxel for 12 weeks
Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University
Budapest, Budapest, Hungary
Residual size of the primary tumor, determined by imaging techniques (in percentage)
Using breast MR measurements, the the residual size of the primary tumor will be specified for all patients (in percentage). The comparison of these between the two study arms will serve as the primary outcome measure. Calculation: The tumor size after the 6-months treatment period (in mm) will be divided by the size measured prior treatment (in mm). The quotient will be given as a percentage and subtracted from 100.
Time frame: change from baseline at 6 months
Percentage of complete pathological response
Comparison of the percentage of complete pathological responses between the two groups
Time frame: 9 months
Treatment response patterns
Comparison of the pathological response categories (pCR : pPR : pNR) between the two groups
Time frame: 9 months
Comparison of surgical procedure ratios
It will be compared whether the ratio of two main breast surgery types (breast-conserving surgery vs. total mastectomy) differ between the two study arms.
Time frame: 9 months
Effect of treatment on white blood cell counts
White blood cell counts (in G/L) will be measeured at every patient visit, and their longitudinal change will be analyzed using mixed-effect statistical modeling techniques.
Time frame: through study completion, an average of ~8 months
Effect of treatment on red blood cell counts
Red blood cell counts (in T/L) will be measeured at every patient visit, and their longitudinal change will be analyzed using mixed-effect statistical modeling techniques.
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added to weekly paclitaxel if patient has triple-negative breast cancer
according to the AC protocol
Either breast-conserving surgery or total mastectomy after the neoadjuvant chemotherapy with or without mEHT (if feasible)
Time frame: through study completion, an average of ~8 months
Effect of treatment on platelet counts
Platelet counts (in G/L) will be measeured at every patient visit, and their longitudinal change will be analyzed using mixed-effect statistical modeling techniques.
Time frame: through study completion, an average of ~8 months
Effect of treatment on hemoglobin levels
Hemoglobin level of patients (in g/L) will be measeured at every patient visit, and their longitudinal change will be analyzed using mixed-effect statistical modeling techniques.
Time frame: through study completion, an average of ~8 months
Effect of treatment on hematocrit levels
Hematocrit level of patients (in L/L) will be measeured at every patient visit, and their longitudinal change will be analyzed using mixed-effect statistical modeling techniques.
Time frame: through study completion, an average of ~8 months
Number of treatments where the planned power output of the Oncotherm EHY-2030 device could not be reached
For an optimal treatment, the Oncotherm EHY-2030 device must reach its maximum output for 30 minutes. The number of treatments where this optimal outpur could not be reached will be reported.
Time frame: 3 months
Longitudinal analysis of the EORTC QLQ-C30 questionnaire's total scores
The European Organisation for Research and Treatment of Cancer 30-item quality of life questionnaire for cancer patients (EORTC QLQ-C30) total scores will be calculated as per the official quidelines, and their longitudinal change will be analyzed using mixed-effect statistical modeling techniques. Scoring of the questionnaire will be performed as per the official instructions of EORTC
Time frame: through study completion, an average of ~8 months
Longitudinal analysis of the EORTC QLQ-BR23 questionnaire's total scores
The European Organisation for Research and Treatment of Cancer 23-item quality of life questionnaire for breast cancer patients (EORTC QLQ-BR23) total scores will be calculated as per the official quidelines, and their longitudinal change will be analyzed using mixed-effect statistical modeling techniques. Scoring of the questionnaire will be performed as per the official instructions of EORTC
Time frame: through study completion, an average of ~8 months
Longitudinal analysis of the EQ-5D-5L questionnaire scores
The questionnaire will be assessed as per official guidelines. EuroQol's 5-dimension health-related quality of life instrument (EQ-5D-5L) questionnaire scores' longitudinal change will be analyzed using mixed-effect statistical modeling techniques. Scoring of the questionnaire will be performed as per the official instructions of EuroQol.
Time frame: through study completion, an average of ~8 months