Neoadjuvant Concomitant Modulated Electro-hyperthermia in HER2-negative Breast Cancer

NCT05889390 | Active Not Recruiting Phase 2

• 1 other identifier: NeoHTerMa
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HER2-negative Breast Cancer

Keywords

hyperthermia; modulated electro-hyperthermia; oncothermia; breast cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  change from baseline at 6 months

Secondary Outcomes (12)

• Percentage of complete pathological response

  9 months

• Treatment response patterns

  9 months

• Comparison of surgical procedure ratios

  9 months

• Effect of treatment on white blood cell counts

  through study completion, an average of ~8 months

• Effect of treatment on red blood cell counts

  through study completion, an average of ~8 months

Other Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  through study completion, an average of ~8 months

Study Arms (2)

wTAX (+ carboplatin) +AC

ACTIVE COMPARATOR

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)

Drug: Paclitaxel; Drug: Carboplatin; Drug: Cyclophosphamide/Doxorubicin; Procedure: Breast cancer removal surgery

wTAX (+ carboplatin) +AC + mEHT

EXPERIMENTAL

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)

Device: Oncotherm EHY-2030; Drug: Paclitaxel; Drug: Carboplatin; Drug: Cyclophosphamide/Doxorubicin; Procedure: Breast cancer removal surgery

Interventions

Oncotherm EHY-2030 DEVICE

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.

wTAX (+ carboplatin) +AC + mEHT

Paclitaxel DRUG

weekly paclitaxel for 12 weeks

wTAX (+ carboplatin) +AC; wTAX (+ carboplatin) +AC + mEHT

Carboplatin DRUG

added to weekly paclitaxel if patient has triple-negative breast cancer

wTAX (+ carboplatin) +AC; wTAX (+ carboplatin) +AC + mEHT

Cyclophosphamide/Doxorubicin DRUG

according to the AC protocol

wTAX (+ carboplatin) +AC; wTAX (+ carboplatin) +AC + mEHT

Breast cancer removal surgery PROCEDURE

Either breast-conserving surgery or total mastectomy after the neoadjuvant chemotherapy with or without mEHT (if feasible)

wTAX (+ carboplatin) +AC; wTAX (+ carboplatin) +AC + mEHT

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• Female patient
• Life expectancy ≥ 6 months
• De novo histological/cytological diagnosis of HER2-negative (triple-negative or ER/PR+) breast tumor involving one breast
• Diagnosis of breast tumor ≤ 40 days
• Locally advanced stage disease (stage II and III) requiring neoadjuvant treatment - according to the following criteria:
• Primary breast tumor ≥ 20 mm in size and/or
• Presence of axillary lymph node metastases
• Optimal surgical intervention without neoadjuvant chemotherapy is not feasible
• ECOG status: 0-2
• Suitable for and designated by the investigator for neoadjuvant therapy with wTAX + (carboplatin) + AC chemotherapeutic agent
• Willingness to participate in the trial and signed the informed consent form for the protocol

You may not qualify if:

• Patient is ≤ 18 years of age.
• Tumor of both breasts.
• Diagnosis of breast tumor \> 40 days
• HER2 positive breast tumor
• Has already received some anticancer therapy
• 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.
• Co-existing serious diseases:
• Presence of severe neuropathy requiring medical treatment, diabetic neuropathy.
• 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.
• 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).
• Uncontrolled hypertension with resting systolic ≥ 180 mmHg, resting diastolic ≥ 110 mmHg.

Sponsors & Collaborators

• Semmelweis University: lead

Study Sites (1)

Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University

Budapest, Budapest, 1083, Hungary

Location

Related Publications (4)

• 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.

  PMID: 31737558 BACKGROUND

• 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.

  PMID: 34616516 BACKGROUND

• 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.

  PMID: 34842668 BACKGROUND

• 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.

  PMID: 36765840 BACKGROUND

MeSH Terms

Conditions

Hyperthermia; Breast Neoplasms

Interventions

Paclitaxel; Carboplatin; AC protocol

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Magdolna Dank, M.D./Ph.D.

  Semmelweis University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. A. Marcell Szasz, PhD, Head of Research at the Department of Internal Medicine and Oncology

Study Record Dates

• First Submitted: March 3, 2023
• First Posted: June 5, 2023
• Study Start: February 20, 2023
• Primary Completion: May 31, 2025
• Study Completion: August 31, 2025
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)