Hyperthermia Combined With Neoadjuvant Radiochemotherapy for LARC

Study Overview
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Brief Summary
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The purpose of this study is to determine whether adding deep hyperthermia to neoadjuvant concurrent radiochemotherapy could improve T-downstaging rate for locally advanced rectal cancer (LARC).

Detailed Description
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The purpose of this study is to determine whether adding deep hyperthermia to neoadjuvant concurrent radiochemotherapy could improve T-downstaging rate for locally advanced rectal cancer (LARC). The sample size is 142. Patients with LARC (T3-4/N+) will be randomly divided into intervention group and control group. For intervention group, the neoadjuvant therapy is hyperthermia combined with concurrent radiochemotherapy. For control group, the neoadjuvant treatment is concurrent radiochemotherapy. T-downstaging rate will be used to evaluate the effectiveness of deep hyperthermia. T-downstaging is defined as the postoperative pathological T stage lower than the original T stage by imaging before treatment.

Official Title
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Deep Hyperthermia Combined With Neoadjuvant Concurrent Radiochemotherapy for Locally Advanced Rectal Cancer, PUTHRC-001：A Multi-Center, Open-Label, Randomized Controlled Study

Conditions
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Hyperthermia, Radiotherapy

Intervention / Treatment
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* Procedure: Deep Hyperthermia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old Pathologically diagnosed as rectal adenocarcinoma Locally advanced rectal cancer (T3-4/N+) staging by CT, MRI and/or endoscopy Males with fertility and females of childbearing age must take effective contraceptive measures at least since signing informed consent until 180 days after the end of concurrent radiotherapy and chemotherapy. Childbearing age means pre-menopausal or within 2 years after menopause. Women of childbearing age must exclude pregnancy before concurrent radiotherapy and chemotherapy Patients with normal organ function prior to treatment, the following criteria are met:a) blood routine examination criteria : i) hemoglobin (HB) ≥90g/L; ii) absolute neutrophil count (ANC) ≥1.5×10e9/L; iii) platelet (PLT) ≥70×10e9/L; b) biochemical tests meet the following criteria: i) serum creatinine (Cr) ≤1.5 times of upper limit of normal (ULN) or creatinine clearance (CCr) ≥40ml/min; ii) total bilirubin (TBIL) ≤1.5 ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ULN, e）Coagulation test: International Normalized Ratio (INR)≤ 1.5 × ULN, Prothrombin Time ≤ 1.5 × ULN Exclusion Criteria: Patients with signet ring cell carcinoma or mucinous adenocarcinoma. Patients who refuse to undergo hyperthermia or cannot cooperate with continuous follow-up. Patients with severe bleeding tendency, severe infection, wounds or infections on the skin of the hyperthermia area. Patients who have metal implants or pacemakers in their bodies who cannot tolerate excessively high temperatures. Other primary malignant tumors occurred within 5 years before concurrent radiotherapy and chemotherapy, except for malignant tumors that have undergone radical treatment and are locally curable (such as basal or squamous cell skin cancer, superficial bladder cancer or prostate, cervical or breast carcinoma in situ, etc.). Suffer from uncontrollable comorbid diseases, including but not limited to symptomatic congestive heart failure, uncontrollable hypertension, unstable angina, arrhythmia, active peptic ulcer or bleeding disease. Patients with a history of alcohol or drug abuse. Patients who do not agree to participate in this study or unable to complete the informed consent process.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperthermia Group<br>The neoadjuvant therapy is hyperthermia combined with concurrent radiochemotherapy for this group. | Procedure: Deep Hyperthermia<br>* Hyperthermia is a type of treatment in which tumor is heated to as high as 40.5-43℃ to help damage and kill cancer cells with little or no harm to normal tissue.<br>|
| No Intervention: Non-hyperthermia group<br>The neoadjuvant treatment is concurrent radiochemotherapy, which is standard treatment for LARC according to the guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor T-downstaging rate | T-downstaging is defined as the postoperative pathological T stage lower than the original T stage by imaging before treatment. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor shrinkage percentage | （tumor volume before treatment-tumor volume before neoadjuvant treatment) /（ tumor volume before neoadjuvant treatment） | 12 weeks | 
| Complete tumor resection rate | （patient number of R0 resection）/（total number of patients undergoing surgery） | 12 weeks | 
| Pathological complete response rate | （number of patients with no residual tumors after neoadjuvant therapy）/（total number of patients undergoing surgery） | 12 weeks | 
| Perioperative complication rate | （number of patients with complications before or after surgery）/（total number of patients undergoing surgery） | 4 months | 
| Anal retention rate | （number of patients with anus preservation after surgery）/（total number of patients undergoing surgery） | 12 weeks | 
| Disease-free survival | the time from random day to disease progression or death (whichever occurs first); | 3 year | 
| Overall survival | the time between a random day and the day of death from any cause. | 3 year | 
| 36-Item Short-Form Health Survey（SF-36） | The minimum and maximum values of SF-36 are 30 and 150. Higher score means a better quality of life. | 3 year | 
| Quality of Life Questionnaire-Core 30（QLQ-C30） | The minimum and maximum values of QLQ-C30 are 0 and 100. Higher score means a better quality of life. | 3year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locally advanced rectal cancer, hyperthermia, neoadjuvant therapy, chemoradiotherapy