Total Neoadjuvant Therapy Combined With Tislelizumab for Local Advanced of Middle and Low Rectal Cancer

Total Neoadjuvant Therapy Combined With Tislelizumab for Local Advanced Phase II Randomized Controlled Clinical Study of Middle and Low Rectal Cancer

This study is a prospective, randomized, open, controlled, multi-center phase II clinical trial, which included patients with locally advanced low rectal cancer as the research object, and evaluated the application of long-term concurrent chemoradiotherapy combined with tislelizumab versus long-term synchronous Efficacy and safety of chemotherapy and radiotherapy as neoadjuvant therapy for patients with locally advanced rectal cancer. The main endpoints of the study were clinical complete response (cCR) (including imaging and endoscopic complete response) and pathological complete response (pathological complete response, pCR). Secondary study endpoints are primary pathological response rate (MPR), objective response rate (ORR), disease-free survival (DFS), overall survival (OS), organ preservation rate (OPR), rectal cancer neoadjuvant therapy score (NAR ), quality of life score (QoL), safety and tolerability. They will be randomly divided into an experimental group (tislelizumab combined with long-term concurrent chemoradiotherapy) and a control group (long-term concurrent chemoradiotherapy) at a ratio of 2:1. Random stratification factors: 1. TNM stage (II/III); 2. Distance from the tumor to the anal verge (≥5cm, <5cm).

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Combination product: Long-course chemoradiation, with Tislelizumab (PD-1 inhibitor); Combination product: Long-course chemoradiation, without Tislelizumab (PD-1 inhibitor)

Detailed Description

This study plans to recruit 102 patients, aged 18-75 years old, male or female; rectal adenocarcinoma confirmed by histopathology; clinical stage II-III assessed by MRI (according to AJCC 8th edition); Margin ≤ 10 cm; surgical resection is possible.All patients should have no history of immune diseases, nor history of immunotherapy or radiotherapy. Eligible participants will be randomly assigned to Experiment Arm (50.4Gy radiation, capecitabine, and anti-PD1 starting at Day 8 of radiation) and Control Arm (50.4Gy radiation, capecitabine) in a 2：1ratio.

• Study Type: Interventional
• Enrollment (Anticipated): 102
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhang Zhongtao, MD; Phone Number: +8613801060364; Email: zhangzht@ccmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
      • Contact: Yao Hongwei, M.D; Phone Number: 86 13611015609; Email: yaohongwei@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients have been fully aware of the content of this study and signed the informed consent voluntarily;
• Patients with rectal cancers must satisfied all the following conditions:Stage II/III LARC (cT3-4aN0M0 and cT1-4aN1-2M0);Tumor distal location ≤ 10 cm from anal verge (MRI diagnosed);
• Patients regardless of gender with aged ≥18 years and ECOG score of 0 or 1;
• Physical and viscera function of patients can withstand major abdominal surgery;
• Patients are willing and able to follow the study protocol during the study;
• Patients give consent to the use of blood and pathological specimens for study;
• Within 28 days prior to enrolment, we must confirm a negative serological pregnancy test for child-bearing age women and they agree to use effective contraception for the duration of drug use and for 60 days after the last dose.

Exclusion Criteria:

• Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time;
• Patients underwent major surgery within 4 weeks prior to study treatment;
• Patients have any condition affects the absorption of capecitabine through gastrointestinal tract;
• Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases;
• Patients who are allergic to any of the ingredients under study;
• Patients with severe concomitant diseases with estimated survival ≤ 5 years;
• Patients with present or previous moderate or severe liver and kidney damage presently or previously;
• Patients have received other study medications or any immunotherapy currently or in the past;
• Patients preparing for or previously received organ or bone marrow transplant;
• Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy;
• Patients with congenital or acquired immune deficiency (such as HIV infection);
• If patients with a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator will determine whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance;
• Patients with other factors that may affect the study results or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment and severe laboratory examination abnormalities.
• Pregnant or lactating women

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
Experimental: CRT+concurrent PD-1 inhibition; Long-course chemoradiation plus PD-1 inhibition (Tislelizumab 200mg, 3 times, 3-week interval) starting on Day 8 of radiation therapy. TME surgery is scheduled in 10~13 weeks after completion of radiation.	Combination product: Long-course chemoradiation, with Tislelizumab (PD-1 inhibitor); Tislelizumab was added to long-course chemoradiotherapy (CRT) in LARC patients, CRT + concurrent tislelizumab was used in the Experimental arm, and CRT was used in the Active Comparator arm.
Active Comparator: CRT without PD-1 inhibition; Long-course chemoradiation plus PD-1 inhibition with no PD-1 inhibition. TME surgery is scheduled in 10~13 weeks after completion of radiation.	Combination product: Long-course chemoradiation, without Tislelizumab (PD-1 inhibitor); Tislelizumab was added to long-course chemoradiotherapy (CRT) in LARC patients, CRT + concurrent tislelizumab was used in the Experimental arm, and CRT was used in the Active Comparator arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	pathological complete response rate	within 10 days after surgery
cCR rate	clinical complete response rate	12-13 weeks after radiotherapy ends

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NAR score	Neoadjuvant rectal（NAR）score：It is based on the scoring criteria of preoperative treatment downstaging. The range is 0-201.46, with higher scores indicating worse prognosis.	within 10 days after surgery
OPR	organ preservation rate	immediately after surgery
ORR	objective response rate	within 10 days after surgery
immune-related adverse event rate	adverse event rate that is deemed to be associated with PD-1 inhibition	up to 30th day after surgery

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Principal Investigator: Zhang Zhongtao, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: April 25, 2023
• First Posted (Estimate): May 5, 2023

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: neoadjuvant; PD-1; chemoradiation; randomized; Tislelizumab; LARC; controlled
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors
• Other Study ID Numbers: BFH-TNT-LARC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Export of individual patient data is a sensitive issue according to current Chinese laws

Drug and device information, study documents

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