Neoadjuvant Concomitant Modulated Electro-hyperthermia in HER2-negative Breast Cancer
NCT ID: NCT05889390
Last Updated: 2024-12-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2/PHASE3
71 participants
INTERVENTIONAL
2023-02-20
2025-08-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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wTAX (+ carboplatin) +AC
1. wTAX: Weekly paclitaxel (+ carboplatin in the case of triple-negative breast cancer) for 12 weeks
2. AC: Doxorubicin/Cyclophosphamide every three-weeks, 4x
3. Breast cancer tumor removal surgery (if feasible)
Paclitaxel
weekly paclitaxel for 12 weeks
Carboplatin
added to weekly paclitaxel if patient has triple-negative breast cancer
Cyclophosphamide/Doxorubicin
according to the AC protocol
Breast cancer removal surgery
Either breast-conserving surgery or total mastectomy after the neoadjuvant chemotherapy with or without mEHT (if feasible)
wTAX (+ carboplatin) +AC + mEHT
1. wTAX + mWEHT
1. wTAX: Weekly paclitaxel (+ carboplatin in the case of triple-negative breast cancer) for 12 weeks
2. mEHT: Concomitant modulated electro-hyperthermia using the Oncotherm EHY-2030 device, 3 times per week, for 12 weeks
2. AC: Doxorubicin/Cyclophosphamide every three-weeks, 4x
3. Breast cancer tumor removal surgery (if feasible)
Oncotherm EHY-2030
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.
Paclitaxel
weekly paclitaxel for 12 weeks
Carboplatin
added to weekly paclitaxel if patient has triple-negative breast cancer
Cyclophosphamide/Doxorubicin
according to the AC protocol
Breast cancer removal surgery
Either breast-conserving surgery or total mastectomy after the neoadjuvant chemotherapy with or without mEHT (if feasible)
Interventions
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Oncotherm EHY-2030
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.
Paclitaxel
weekly paclitaxel for 12 weeks
Carboplatin
added to weekly paclitaxel if patient has triple-negative breast cancer
Cyclophosphamide/Doxorubicin
according to the AC protocol
Breast cancer removal surgery
Either breast-conserving surgery or total mastectomy after the neoadjuvant chemotherapy with or without mEHT (if feasible)
Eligibility Criteria
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Inclusion Criteria
2. Female patient
3. Life expectancy ≥ 6 months
4. De novo histological/cytological diagnosis of HER2-negative (triple-negative or ER/PR+) breast tumor involving one breast
5. Diagnosis of breast tumor ≤ 40 days
6. Locally advanced stage disease (stage II and III) requiring neoadjuvant treatment - according to the following criteria:
1. Primary breast tumor ≥ 20 mm in size and/or
2. Presence of axillary lymph node metastases
3. Optimal surgical intervention without neoadjuvant chemotherapy is not feasible
7. ECOG status: 0-2
8. Suitable for and designated by the investigator for neoadjuvant therapy with wTAX + (carboplatin) + AC chemotherapeutic agent
9. Willingness to participate in the trial and signed the informed consent form for the protocol
Exclusion Criteria
2. Tumor of both breasts.
3. Diagnosis of breast tumor \> 40 days
4. HER2 positive breast tumor
5. Has already received some anticancer therapy
6. Any previous cancer requiring anti-tumor treatment within 5 years prior to selection, except: in situ cervical or uterine cancer and non-melanoma skin cancer.
7. Co-existing serious diseases:
1. Presence of severe neuropathy requiring medical treatment, diabetic neuropathy.
2. Clinically significant hematological, hepatic or renal dysfunction, as defined below:
* Neutrophil count \< 1.5 G/L and platelet count \< 100 G/L
* bilirubin \> 1.5 times the upper limit of normal range (ULN), except for known Gilbert's disease
* AST and/or ALT \> 2.5 times the upper limit of the normal range
* Serum creatinine \> 1.5 times the upper limit of the normal range.
3. Clinically significant cardiovascular disease in the medical history, unless the disease is adequately controlled. E.g. New York Heart Association (NYHA) Class II or worse congestive heart failure (moderate limitation of physical activity; well-being at rest but normal activity is associated with fatigue, rapid heart rate or dyspnoea).
4. Uncontrolled hypertension with resting systolic ≥ 180 mmHg, resting diastolic ≥ 110 mmHg.
5. Resting sinus tachycardia with a pulse ≥ 110/min.
6. History of sympathetic or treatment-naive cardiac arrhythmia. Atrial fibrillation or flutter controlled with medication is not an exclusion for participation in the study.
7. Major cardiovascular event (e.g. myocardial infarction, unstable angina, cerebral vascular accident (CVA), etc.) in the 6 months prior to randomisation.
8. Active infection or severe underlying disease that renders the patient unfit for treatment according to the study protocol.
* A current diagnosis of chronic hepatitis, Hepatitis B surface antigen positive, Hepatitis C antibody positive and/or other clinically active liver disease requiring treatment.
* Known HIV infection.
* Untreated thyroid disease.
* Systemic autoimmune disease.
9. Any psychiatric condition in the medical history that may result in the patient being unable to understand or comply with the requirements of the study, having reduced communication skills or being unable to give informed consent.
8. Need for concomitant anti-tumor therapy in addition to wTAX + (carboplatin) + AC protocol
9. Any active medical device implanted in the anatomical area, such as pacemakers.
10. Known severe hypersensitivity to any of the chemotherapies used in the study.
11. Pregnancy or breast-feeding (patients of childbearing potential must use effective contraception throughout the study and for 3 months after the end of treatment). The method of effective contraception is at the discretion of the investigator.
12. History of drug or alcohol dependence within 6 months prior to screening.
13. Unable to comply with the study plan for medical, psychological, family, geographical or other reasons.
14. Institutionalisation by administrative or judicial decision.
18 Years
FEMALE
No
Sponsors
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Semmelweis University
OTHER
Responsible Party
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Marcell Szasz
Dr. A. Marcell Szasz, PhD, Head of Research at the Department of Internal Medicine and Oncology
Principal Investigators
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Magdolna Dank, M.D./Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Semmelweis University
Locations
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Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University
Budapest, Budapest, Hungary
Countries
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References
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Szasz AM, Minnaar CA, Szentmartoni G, Szigeti GP, Dank M. Review of the Clinical Evidences of Modulated Electro-Hyperthermia (mEHT) Method: An Update for the Practicing Oncologist. Front Oncol. 2019 Nov 1;9:1012. doi: 10.3389/fonc.2019.01012. eCollection 2019.
Herold Z, Szasz AM, Dank M. Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system. World J Gastrointest Oncol. 2021 Sep 15;13(9):1109-1120. doi: 10.4251/wjgo.v13.i9.1109.
Petenyi FG, Garay T, Muhl D, Izso B, Karaszi A, Borbenyi E, Herold M, Herold Z, Szasz AM, Dank M. Modulated Electro-Hyperthermic (mEHT) Treatment in the Therapy of Inoperable Pancreatic Cancer Patients-A Single-Center Case-Control Study. Diseases. 2021 Nov 3;9(4):81. doi: 10.3390/diseases9040081.
Szasz AM, Arrojo Alvarez EE, Fiorentini G, Herold M, Herold Z, Sarti D, Dank M. Meta-Analysis of Modulated Electro-Hyperthermia and Tumor Treating Fields in the Treatment of Glioblastomas. Cancers (Basel). 2023 Jan 31;15(3):880. doi: 10.3390/cancers15030880.
Other Identifiers
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NeoHTerMa
Identifier Type: -
Identifier Source: org_study_id