Trial Title:
Neoadjuvant Concomitant Modulated Electro-hyperthermia in HER2-negative Breast Cancer
NCT ID:
NCT05889390
Condition:
HER2-negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Hyperthermia
Fever
Paclitaxel
Cyclophosphamide
Carboplatin
Doxorubicin
Conditions: Keywords:
hyperthermia
modulated electro-hyperthermia
oncothermia
breast cancer
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Device
Intervention name:
Oncotherm EHY-2030
Description:
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.
Arm group label:
wTAX (+ carboplatin) +AC + mEHT
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
weekly paclitaxel for 12 weeks
Arm group label:
wTAX (+ carboplatin) +AC
Arm group label:
wTAX (+ carboplatin) +AC + mEHT
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
added to weekly paclitaxel if patient has triple-negative breast cancer
Arm group label:
wTAX (+ carboplatin) +AC
Arm group label:
wTAX (+ carboplatin) +AC + mEHT
Intervention type:
Drug
Intervention name:
Cyclophosphamide/Doxorubicin
Description:
according to the AC protocol
Arm group label:
wTAX (+ carboplatin) +AC
Arm group label:
wTAX (+ carboplatin) +AC + mEHT
Intervention type:
Procedure
Intervention name:
Breast cancer removal surgery
Description:
Either breast-conserving surgery or total mastectomy after the neoadjuvant chemotherapy
with or without mEHT (if feasible)
Arm group label:
wTAX (+ carboplatin) +AC
Arm group label:
wTAX (+ carboplatin) +AC + mEHT
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. At least 18 years of age
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:
1. Patient is ≤ 18 years of age.
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.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University
Address:
City:
Budapest
Zip:
1083
Country:
Hungary
Status:
Recruiting
Contact:
Last name:
Attila M Szasz, M.D./Ph.D.
Phone:
+3614591500
Phone ext:
51618
Email:
szasz.attila_marcell@med.semmelweis-univ.hu
Contact backup:
Last name:
Zoltan Herold, Ph.D.
Phone:
+3614591500
Email:
herold.zoltan@med.semmelweis-univ.hu
Investigator:
Last name:
Magdolna Dank, M.D./Ph.D.
Email:
Principal Investigator
Investigator:
Last name:
Gyöngyvér Szentmártoni, M.D./Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Magdolna Herold
Email:
Sub-Investigator
Start date:
February 20, 2023
Completion date:
April 30, 2025
Lead sponsor:
Agency:
Semmelweis University
Agency class:
Other
Source:
Semmelweis University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05889390
