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.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Down-staging Rate
研究概览
简要总结
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.
详细描述
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℃.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •7. ECOG performance status: 0 - 2
- •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
- •Willingness to participate in the clinical trial and signed the informed consent form for the protocol.
排除标准
- •(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
- •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
- •Known allergic reaction to trial medications
- •Pregnant or breastfeeding women
- •Substance or alcohol dependence within six months before screening
- •Inability to comply with treatment, assessments, or follow-up
研究组 & 干预措施
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.
干预措施: Hyperthermia (Device)
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.
结局指标
主要结局
Down-staging Rate
时间窗: 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.
次要结局
- 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.)
- Distant Metastasis-Free Survival (DMFS)(12, 36, 60 months from the date of randomization)
- Colostomy-Free Survival (CFS)(12, 36, 60 months from the date of randomization.)
- Comparison of Surgery Rates(12 months)
- Surgical Techniques(12 months)
- Number of Hyperhermia(9 months)
- Adverse Effects Assessment(2, 36, 60 months)
- The effect of treatment on white blood cell count(2, 36, 60 months)
- The effect of treatment on hemoglobin level(2, 36, 60 months)
- The effect of treatment on platelet count(2, 36, 60 months)
- Late Radiation Therapy Adverse Effects(36, 60 months)
- Quality of Life Analysis(12 months.)
- Rectal Cancer Quality of Life Analysis(12 months.)
- Functional Assessment Post Rectal Cancer Surgery(12 months)
研究者
Shih-Kai Hung
Director of Radiation Oncology
Dalin Tzu Chi General Hospital