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

NCT07372300 | Recruiting Phase 3

• 1 other identifier: iIRB No. A11304001
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Locally Advanced Rectal Carcinoma

Keywords

Rectal cancer; Hyperthermia; Neoadjuvant; Radiotherapy; Downstaging

Outcome Measures

Primary Outcomes (1)

• Down-staging Rate

  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 Outcomes (18)

• Pathological Complete Response (pCR) Rate.

  9 months from the date of randomization

• Treatment Response Patterns

  9 months

• Overall Survival (OS)

  12, 36, 60 months from the date of randomization

• Disease-Free Survival (DFS)

  12, 36, 60 months from the date of randomization

• Local Control Rate (LCR)

  Time Frame: 12, 36, 60 months from the date of randomization.

Study Arms (2)

TNT + mEHT

EXPERIMENTAL

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

TNT alone

NO INTERVENTION

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.

Interventions

Hyperthermia DEVICE

Modulated electro-hyperthermia, 2 times weekly for 6 weeks

TNT + mEHT

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 20 years and above
• Gender: Not restricted
• Initial pathological diagnosis of adenocarcinoma of the rectum
• Expected survival ≥ six months
• 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 \[staging system according to the 8th edition of the AJCC staging manual\]:
• cT3: Tumor invades through the muscularis propria into pericolorectal tissues
• 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)
• 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.
• \. 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.

You may not qualify if:

• (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

Sponsors & Collaborators

• Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation: collaborator
• Shih-Kai Hung: lead

Study Sites (1)

Dalin Tzu Chi Hospital

Chiayi City, Dalin Township, 600401, Taiwan

RECRUITING

Related Publications (19)

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Related Links

• Network NCC. Rectal Cancer (Version 2.2024).

MeSH Terms

Conditions

Rectal Neoplasms; Hyperthermia

Interventions

Diathermy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Hyperthermia, Induced; Therapeutics

Central Study Contacts

Pei-Yu Hsu, Master

CONTACT

+886+5+2648000; dorishsu1071013@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Radiation Oncology

Study Record Dates

• First Submitted: January 8, 2026
• First Posted: January 28, 2026
• Study Start: September 23, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)