Modulated Electro-Hyperthermia in Combination With Multimodal Therapy for Locally Advanced Rectal Cancer (mEHT)

January 19, 2026 updated by: Shih-Kai Hung

The Efficacy of Combination of Modulated Electro-Hyperthermia(mEHT) in The Multimodality Management in Locally Advanced Rectal Cancer: A Multicenter Phase 3 Randomized Control Trial.

The goal of this clinical trial is to investigate if the addition of modulated electro-hyperthermia (mEHT) improves tumor down-staging and pathological response in adult patients (20 years and above) with locally advanced rectal adenocarcinoma (cT3N0M0 with high risk of recurrence, cT3N1-2M0, or cT4N0-2M0). The main questions it aims to answer are:

  • Does the addition of mEHT to the Total Neoadjuvant Therapy (TNT) regimen significantly increase the rate of tumor down-staging (ypT and ypN) compared to TNT alone?
  • Does the combination therapy improve the pathological complete response (pCR) rate and long-term outcomes (such as disease-free survival) compared to standard TNT?

Researchers will compare participants randomized to receive Total Neoadjuvant Therapy (TNT) plus mEHT using the Oncotherm EHY-2030 device to participants receiving TNT alone to see if the adjunctive mEHT therapy enhances tumor regression and improves patient prognosis. Participants will be randomized (1:1) into one of the two groups and will undergo the following regimen:

  • Receive standard TNT, which includes 5-6 weeks of chemoradiotherapy (CRT) followed by 4-6 months of neoadjuvant chemotherapy.
  • Patients in the experimental group will receive mEHT twice a week during the CRT period.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is designed as a pivotal Phase 3, open-label, two-treatment group, multi-institute randomized control trial (1:1).

Study Population & Allocation:

Participants with pathologically confirmed rectal adenocarcinoma who are recommended for TNT by a specialist surgeon will be included. Patients are randomly allocated (1:1) into either the Experimental Arm (TNT + mEHT combination) or the Control Arm (TNT alone).

Intervention and Device:

Modulated electro-hyperthermia (mEHT, trade name Oncotherm) will be delivered using the Oncotherm EHY-2030 device. This technique uses electromagnetic waves at 13.56 MHz and incorporates a low-frequency current wave to deliver energy selectively to the cancerous area. The Oncotherm computer system automatically adjusts the optimal frequency, introducing random resonance to heat the tumor tissue and improve the tumor microenvironment. Local hyperthermia is intended to control tumors by raising the local body temperature to 39℃-42℃.

We hypothesized that the combination of hyperthermia with other treatments (such as radiotherapy and chemotherapy) can improve treatment outcome without additional toxicity. Patients in the Experimental Arm will receive mEHT twice a week specifically during the CRT period.

Study Type

Interventional

Enrollment (Estimated)

126

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Taiwan
    • Dalin Township
      • Chiayi City, Dalin Township, Taiwan, 600401
        • Recruiting
        • Dalin Tzu Chi Hospital
        • Contact:
        • Principal Investigator:
          • Shih Kai Hung, Doctor's degree

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age: 20 years and above
  2. Gender: Not restricted
  3. Initial pathological diagnosis of adenocarcinoma of the rectum
  4. Expected survival ≥ six months

  5. Clinical staging of cT3N0 with high recurrence risk or cT3N1-2 or cT4N0-2 rectal cancer, requiring neoadjuvant therapy, without distant metastasis; must meet the following tumor definitions [staging system according to the 8th edition of the AJCC staging manual]:

    1. cT3: Tumor invades through the muscularis propria into pericolorectal tissues
    2. cT4a: Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum)
    3. cT4b: Tumor directly invades or adheres to adjacent organs or structures *High recurrence risk factors: cT3 tumor ≤ 5 cm from the anal verge or MRI showing circumferential resection margin (CRM) < 0.2 cm; cT4 tumor or cN2, presence of MRI showing extramural vascular invasion.

7. ECOG performance status: 0 - 2 8. Healthy condition suitable for standard treatment, including 25 to 30 fractions of long-course radiotherapy and concurrent chemotherapy (capecitabine or fluorouracil) and subsequent 4- to 6-month chemotherapy, including modified FOLFOX-6 or CAPEOX 9. Willingness to participate in the clinical trial and signed the informed consent form for the protocol.

Exclusion Criteria:

  • (e) Active infection or severe underlying disease making the patient unsuitable for the trial treatments
  • Known HIV infection
  • Untreated thyroid disease
  • Active Crohn's disease or ulcerative colitis
  • Other systemic autoimmune diseases 9. History of any physical or mental disorder resulting the patient unable to understand or comply with trial requirements, or diminished social communication ability, or unable to provide informed consent 10. Known allergic reaction to trial medications 11. Pregnant or breastfeeding women 12. Substance or alcohol dependence within six months before screening 13. Inability to comply with treatment, assessments, or follow-up

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TNT + mEHT

Participants receive standard TNT with modulated electro-hyperthermia (mEHT). This includes long-course CRT with concurrent mEHT, twice weekly, for 5-6 weeks, followed by neoadjuvant chemotherapy (4-6 months), and finally surgery.

Chemoradiation therapy phase Drug: Capecitabine or Tegafur/ Uracil or Fluorouracil (5-FU) + Leucrorin (LV) concomitant with RT Procedure: Radiotherapy Total radiation dose of 45-50.4 Gy delivered in 25-28 fractions to the pelvis, and the dose of 52-56 Gy for gross tumor volumes and positive lymph nodes.

Device: Oncotherm Modulated EHY-2030 Oncotherm device is working on a radiofrequency of 13.56 MHz. Treatments are administered twice weekly during the 5-6-week CRT phase. Each session lasts 60 minutes

Neoadjuvant systemic therapy:

4-6 months of neoadjuvant chemotherapy using CAPEOX or mFOLFOX 6 regimens following CRT

Surgery:

Total mesorectal excision (TME) performed after the completion of neoadjuvant chemotherapy.
Device: Hyperthermia
Modulated electro-hyperthermia, 2 times weekly for 6 weeks
No Intervention: TNT alone

Participants receive standard TNT without modulated electro-hyperthermia (mEHT).

This includes long-course CRT with concurrent mEHT, twice weekly, for 5-6 weeks, followed by neoadjuvant chemotherapy (4-6 months), and finally surgery.

Chemoradiation therapy phase Drug: Capecitabine or Tegafur/ Uracil or Fluorouracil (5-FU) + Leucrorin (LV) concomitant with RT Procedure: Radiotherapy Total radiation dose of 45-50.4 Gy delivered in 25-28 fractions to the pelvis, and the dose of 52-56 Gy for gross tumor volumes and positive lymph nodes.

Device: Oncotherm Modulated EHY-2030

Neoadjuvant systemic therapy:

4-6 months of neoadjuvant chemotherapy using CAPEOX or mFOLFOX 6 regimens following CRT

Surgery:

Total mesorectal excision (TME) performed after the completion of neoadjuvant chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Down-staging Rate
Time Frame: Time Frame: 9 months from the date of randomization
Evaluation of the decrease in ypT and ypN staging for patients with locally advanced rectal cancer following the current recommended treatment method, total neoadjuvant therapy (TNT). The ycT and ycN staging will be assessed using MRI within three months post-treatment for patients who do not undergo surgery.
Time Frame: 9 months from the date of randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response (pCR) Rate.
Time Frame: 9 months from the date of randomization

A pCR must include no gross or microscopic tumor identified anywhere within the surgical specimen. This must include:

  • No evidence of malignant cells in the primary tumor specimen AND
  • No evidence of malignant cells in the lymph nodes.
9 months from the date of randomization
Treatment Response Patterns
Time Frame: 9 months
Using the Dworak Scale, defined as "good tumor shrinkage" with Grade 3 and Grade 4.
9 months
Overall Survival (OS)
Time Frame: 12, 36, 60 months from the date of randomization
OS is defined as time from randomization to the date of death due to any cause.
12, 36, 60 months from the date of randomization
Disease-Free Survival (DFS)
Time Frame: 12, 36, 60 months from the date of randomization
DFS is defined as the time from randomization to the date of local recurrence, regional recurrence, distant recurrence or death due to all causes whichever comes first. Patients who fail to return for evaluation after beginning therapy will be censored for DFS on the last day of therapy.
12, 36, 60 months from the date of randomization
Local Control Rate (LCR)
Time Frame: Time Frame: 12, 36, 60 months from the date of randomization.
LCR is defined as the time from randomization to the date of the first documentation of local recurrence.
Time Frame: 12, 36, 60 months from the date of randomization.
Distant Metastasis-Free Survival (DMFS)
Time Frame: 12, 36, 60 months from the date of randomization
DMFS is defined as the time from randomization to the date of the first documentation of distant metastasis.
12, 36, 60 months from the date of randomization
Colostomy-Free Survival (CFS)
Time Frame: 12, 36, 60 months from the date of randomization.
CFS is defined as being alive without a colostomy, excluding colostomies reversed during follow-up.
12, 36, 60 months from the date of randomization.
Comparison of Surgery Rates
Time Frame: 12 months
Comparison of Surgery Rates is defined as the rate of patients who receive TME between two groups after TNT.
12 months
Surgical Techniques
Time Frame: 12 months
Surgical Techniques to be recorded: Total Mesorectal Excision (TME), local excision or other (specify).
12 months
Number of Hyperhermia
Time Frame: 9 months
For the optimal treatment, patients in experimental arm receive hyperthermia by using Oncotherm EHY-2030 device, with a planned power output of 60 minutes. The number of treatment where this optimal output could not be reached must be recorded and reported.
9 months
Adverse Effects Assessment
Time Frame: 2, 36, 60 months
Using CTCAE v5.0, scored 0 - 5, with higher scores indicating more severe adverse effects. The items include: radiation dermatitis, anorexia, nausea, vomiting, constipation, diarrhea, dysuria, hematuria, and fatigue. All items are planned to be evaluated at the initiation of treatment (week 1), and subsequently at the week 6, week 9, week 28, week 42, week 48, week 60, week 72, week 84, and week 96 (+/- 3 weeks is permitted).
2, 36, 60 months
The effect of treatment on white blood cell count
Time Frame: 2, 36, 60 months
Recording total white cell counts, absolute neutrophil counts, and absolute lymphocyte counts of all patients. Blood samples are obtained at the initiation of treatment (week 1), and subsequently at the week 6, week 9, week 28, week 42, week 48, week 60, week 72, week 84, and week 96 (+/- 3 weeks is permitted).
2, 36, 60 months
The effect of treatment on hemoglobin level
Time Frame: 2, 36, 60 months
Recording hemoglobin levels of all patients. Blood samples are obtained at the initiation of treatment (week 1), and subsequently at the week 6, week 9, week 28, week 42, week 48, week 60, week 72, week 84, and week 96 (+/- 3 weeks is permitted).
2, 36, 60 months
The effect of treatment on platelet count
Time Frame: 2, 36, 60 months
Recording platelet counts of all patients. Blood samples are obtained at the initiation of treatment (week 1), and subsequently at the week 6, week 9, week 28, week 42, week 48, week 60, week 72, week 84, and week 96 (+/- 3 weeks is permitted).
2, 36, 60 months
Late Radiation Therapy Adverse Effects
Time Frame: 36, 60 months
Using the LENT/SOMA scoring system, evaluating symptoms such as tenesmus, mucosal loss, sphincter control, stool frequency, pain, bleeding, ulceration, stricture, etc., scored 1 - 4, with higher scores indicating worse outcomes.
36, 60 months
Quality of Life Analysis
Time Frame: 12 months.

Quality of Life (QoL) assessment is mandatory for all eligible patients randomized into the trial. QoL will be evaluated using the total score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). A printed questionnaire will be administered in the clinic by a CRA or study nurse at the following time points:

  • Baseline (at the time of randomization, prior to treatment initiation).
  • The last week of neoadjuvant CRT with or without mEHT.
  • Nine months after the completion of the TNT course (approximately 42 weeks ± 3 weeks post-randomization).
12 months.
Rectal Cancer Quality of Life Analysis
Time Frame: 12 months.

Rectal Cancer Quality of Life (QoL) assessment is mandatory for all eligible patients randomized into the trial. QoL will be evaluated using the total score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-CR29). A printed questionnaire will be administered in the clinic by a CRA or study nurse at the following time points:

  • Baseline (at the time of randomization, prior to treatment initiation).
  • The last week of neoadjuvant CRT with or without mEHT.
  • Nine months after the completion of the TNT course (approximately 42 weeks ± 3 weeks post-randomization).
12 months.
Functional Assessment Post Rectal Cancer Surgery
Time Frame: 12 months

Using the LAR score.

The QoL evaluation focus on functional outcome will be evaluated using LAR score. This assessment is mandatory for all eligible patients randomized into the trial. A printed questionnaire will be administered in the clinic by a CRA or study nurse at the following time points:

  • Baseline (at the time of randomization, prior to treatment initiation).
  • The last week of neoadjuvant CRT with or without mEHT.
  • Nine months after the completion of the TNT course (approximately 42 weeks ± 3 weeks post-randomization).
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shih-Kai Hung

Collaborators

Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2025

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

January 8, 2026

First Submitted That Met QC Criteria

January 19, 2026

First Posted (Actual)

January 28, 2026

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 19, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • iIRB No. A11304001 (Other Identifier: Dalin Tzu Chi Hospital - Research Ethics Committee)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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