Hyperthermic Intraperitoneal Treatment of rmhTNF for CRCPM: Phase II Clinical Trial

Hyperthermic Intraperitoneal Treatment of Recombinant Modified Human Tumor Necrosis Factor (rmhTNF) for Colorectal Cancer With Peritoneal Metastases: Phase II Clinical Trial

The goal of this study is planing to adopt intra-abdominal perfusion therapy of rmhTNF during radical colorectal cancer surgery to determine whether intra-abdominal therapy has an impact on postoperative intestinal function recovery, anastomotic leakage, postoperative bleeding, postoperative adhesion intestinal obstruction and other complications. On this basis, the effect of rmhTNF on postoperative peritoneal implantation metastasis and long-term survival was further studied. The main question it aims to answer is: To evaluate the safety and efficacy of rmhTNF in the treatment of peritoneal metastases in colorectal cancer. Participants will receive 1. Radical surgery: Surgical methods can be developed or endoscopic (including robotic surgery). Radical resection of colorectal cancer (corresponding resection of colon and rectum plus regional lymph node dissection, regional lymph node dissection including parenteral, intermediate and mesangial root lymph nodes) follows the principle of mesangectomy and tumorless operation. 2. Abdominal heat perfusion was performed twice: the first time, 5 million IUrmhTNF, dissolved in 30-50ml normal saline, was intraperitoneal heat perfusion into the surgical focus after the operation; the second time, rhatitrexed 2.5mg/m2 was injected into the abdominal cavity through thermoperfusion or drainage tube; 3. Postoperative systemic chemotherapy regimen: postoperative adjuvant chemotherapy should be started 3-4 weeks after surgery, and appropriately extended for patients with poor physique, but no later than 8 weeks after surgery. The chemotherapy regimen was determined by the clinician according to pathological stage, molecular typing, and risk factors, referring to the NCCN and CSCO guidelines.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Peritoneal Metastases
• Intervention / Treatment: Drug: Hyperthermic intraperitoneal treatment of recombinant modified human tumor necrosis factor (rmhTNF)

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lifeng Sun, Dr.; Phone Number: 139 5810 3041; Email: sunlifeng@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Lifeng Sun, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adenocarcinoma of colonic and peritoneal reflexive superior rectum was confirmed by pathology, aged 18-70 years;
• Body condition score (PS) 0 ~ 1 in the Eastern Tumor Collaboration Group (ECOG);
• Preoperative clinical stage was M1c;
• No neoadjuvant therapy was performed;
• Histopathologically confirmed as peritoneal metastases of colorectal cancer > 10cm from the anus, R0-resected, adenocarcinoma/mucinous adenocarcinoma
• The functions of vital organs shall meet the following requirements;
• Be able to understand the situation of this study and sign informed consent.

Exclusion Criteria:

• Allergic history of TNF and its derivatives;
• Patients with fever (>38℃);
• Active hepatitis and peripheral neuropathy (e.g., peripheral neuritis, pseudomeningitis, motor neuritis, and sensory disorders);
• Pregnant or lactating women, or potentially pregnant women and sexually active men who refuse/cannot receive medically acceptable forms of contraception;
• Patients with a history of malignant tumor;
• Clinical symptoms or diseases of the heart that are not well controlled.
• Subject has any active autoimmune disease or history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitaritis, vasculitis, nephritis, hyperthyroidism, hypothyroidism;
• The subject has a known history of psychotropic substance abuse, alcoholism or drug use; Subjects innate or acquired immune function defects (such as HIV infection), or active hepatitis
• Other conditions in which the investigator thinks the patient should not participate in the study;
• A history of neurological or psychiatric disorders, such as major depression or dementia, that may affect the informed study or follow-up evaluation;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group1; The preoperative clinical stage was M1c colon or peritoneal retroflex superior rectum adenocarcinoma	Drug: Hyperthermic intraperitoneal treatment of recombinant modified human tumor necrosis factor (rmhTNF); 5 million IUrmhTNF, dissolved in 30-50ml normal saline, was intraperitoneal heat perfusion into the surgical focus after the operation;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0, the time of postoperative intestinal function recovery, whether exist anastomotic leakage, postoperative bleeding, postoperative adhesion ileus, and other complications in 2 weeks after surgery.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the recurrence rate of metastasis and long-term survival of participants accepted the treatment of rmhTNF in the treatment of peritoneal metastases in colorectal cancer.	record the time period between the date of randomization and the date of patient tumor recurrence or death (earliest occurrence), and calculated the recurrence rate of metastasis after surgery.; 1-year overall survival rate after surgery	1 year

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Shanghai Weike Biopharmaceutical Co., Ltd.
• Investigators: Study Chair: Lifeng Sun, Dr, 2ndAffiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2023
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: March 2, 2023
• First Posted (Estimate): March 6, 2023

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Peritoneal metastasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 2022-0966

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No