Hyperthermia Combined With Neoadjuvant Radiochemotherapy for LARC (PUTHRC-001)

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Hyperthermia; Radiotherapy
• Intervention / Treatment: Procedure: Deep Hyperthermia

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 142
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hao Wang, Doctor; Phone Number: 82264911; Email: wanghaobysy@bjmu.edu.cn
• Study Contact Backup: Name: Yuxia Wang; Phone Number: 82265968; Email: lily31415926@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hyperthermia Group; The neoadjuvant therapy is hyperthermia combined with concurrent radiochemotherapy for this group.	Procedure: Deep Hyperthermia; 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.
NO_INTERVENTION: Non-hyperthermia group; The neoadjuvant treatment is concurrent radiochemotherapy, which is standard treatment for LARC according to the guidelines.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Beijing Friendship Hospital; Beijing Chao Yang Hospital
• Investigators: Study Director: Hao Wang, Doctor, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2022
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2024

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (ACTUAL): October 7, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 7, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: hyperthermia; neoadjuvant therapy; chemoradiotherapy; locally advanced rectal cancer
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever
• Other Study ID Numbers: PUTHRC-001

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