Neoadjuvant Chemoradiation Therapy Combined With Immunotherapy for MSS Ultra-low Rectal Cancer

Multicenter Prospective Randomized Clinical Trial of Neoadjuvant Chemoradiation Therapy Combined With Immunotherapy for MSS Ultra-low Rectal Cancer

At present, there are no relevant studies or reports on the effect of neoadjuvant chemoradiation therapy combined with immunotherapy for MSS ultra-low rectal cancer. Studied in this paper combin neoadjuvant chemoradiation with immune therapy, carry out "Multicenter prospective randomized clinical trial of neoadjuvant chemoradiation therapy combined with immunotherapy for MSS ultra-low rectal cancer" in order to provide a high-level evidence-based medical evidence for ultra-low rectal cancer treatment and improve ultra-low rectal cancer diagnosis and treatment effect.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer; Microsatellite Instability Low; Immunotherapy; Neoadjuvant Chemoradiation Therapy
• Intervention / Treatment: Other: Control; Drug: xintilimab injection

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Department of Colorectal Surgery in Changhai Hospital
      • Contact: Wei Zhang; Phone Number: 021-31161613; Email: weizhang2000cn@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Ultra low rectal cancer patients evaluated by multidisciplinary team to perform APR

• Patients who have a strong desire to preserve the anus and are willing to accept neoadjuvant treatment
• 18 years old ≤ age ≤ 75 years old, no gender limit;
• Colonoscopy, intracavitary ultrasound and pelvic high-resolution MRI (or enhanced CT) were diagnosed as extremely low rectal cancer within 5 cm from the lower edge of the tumor to the anal edge. The baseline clinical stage is T1-3aN0-1M0, and the size of the tumor <1/2 circle;
• Histopathological diagnosis of rectal adenocarcinoma; tumor biopsy immunohistochemistry showed pMMR, that is, MSH1, MSH2, MSH6 and PMS2 four proteins are positive, or genetic testing suggests MSI-L or MSS.
• The patient has good compliance and can come to the hospital for reexamination as required;
• ECOG physical status score 0-1 points;
• Have not received anti-tumor and immunotherapy before being selected;
• 8. Laboratory inspections must meet the following standards: i. White blood cell count ≥3.5×109/L, absolute neutrophil count ≥1.8×109/L, platelet count ≥100×10^9/L, hemoglobin ≥100g/L; ii. INR≤1.5, and APTT≤1.5 times the upper limit of normal value or partial prothrombin time (PTT)≤1.5 times the upper limit of normal value; iii. Total bilirubin≤1.25 times the upper limit of normal; ALT and AST≤5 times the upper limit of normal; iv. 24h creatinine clearance rate ≥50mL/min or blood creatinine ≤1.5 times the upper limit of normal.
• Voluntarily sign the informed consent form;

Exclusion Criteria:

• History of other malignant diseases in the past 5 years;
• Patients with metastases ;
• Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. who need emergency surgery;
• Those who are known to be allergic to capecitabine, oxaliplatin, PD-1 monoclonal antibody and other drugs;
• Patients with poorly differentiated adenocarcinoma, signet ring cell carcinoma, and mucinous adenocarcinoma;
• The patient is accompanied by any unstable systemic diseases, including but not limited to: severe infection, uncontrolled diabetes, hypertension that cannot be controlled by drugs, unstable angina, cerebrovascular accident or transient cerebral ischemia, myocardium Infarction, congestive heart failure, severe arrhythmia requiring medication, liver, kidney or metabolic diseases; diseases that affect the life of the patient.
• The patient's accompanying diseases (such as mental illness, etc.) or conditions (such as alcohol or drug abuse, etc.) will increase the patient's risk of receiving experimental drug treatment or affect the patient's compliance with the trial requirements, or may confuse the research results;
• Within 30 days before screening, the patient has received any other experimental drug treatment or participated in another interventional clinical trial;
• Women who are pregnant or breastfeeding or who intend to become pregnant or breastfeeding during the study period; men or women who are unwilling to take effective contraceptive measures;
• The investigator judges that the patient is not suitable to participate in other situations such as the clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: neoadjuvant chemoradiation therapy	Other: Control; neoadjuvant chemoradiation therapy
Experimental: neoadjuvant chemoradiation therapy +immunotherapy	Drug: xintilimab injection; neoadjuvant chemoradiation therapy +xintilimab injection 200mg/3week 4cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of cCR	Rate of patients who achieve clinical complete response	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of organ preservation	Rate of patients who achieve organ preservation	2 years
The rate of anus preservation	Rate of patients who achieve anus preservation	2 years
pCR rate	Rate of pCR patients after surgery	2 years
Disease free survival(DFS)	DFS was defined as the duration from the date of randomization to the date of the first recurrence (local, distant, or mixed) or death.	2 years
overall survival(OS)	OS was calculated from the date of randomization.	2 years
quality of life	The QoL was assessed by EORTC QOL Core Questionnaire.	2 years

Collaborators and Investigators

• Sponsor: Changhai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: January 18, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Genomic Instability; Rectal Neoplasms; Microsatellite Instability
• Other Study ID Numbers: CHCRS-Immunity

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD would be available upon reasonable request.
• IPD Sharing Time Frame: 2 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No