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

NCT05845268 | Unknown Phase 2 DMC

• 1 other identifier: BFH-TNT-LARC
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Locally Advanced Rectal Cancer

Keywords

neoadjuvant; Tislelizumab; PD-1; chemoradiation; LARC; randomized; controlled

Outcome Measures

Primary Outcomes (2)

• pCR rate

  pathological complete response rate

  within 10 days after surgery

• cCR rate

  clinical complete response rate

  12-13 weeks after radiotherapy ends

Secondary Outcomes (4)

• NAR score

  within 10 days after surgery

• OPR

  immediately after surgery

• ORR

  within 10 days after surgery

• immune-related adverse event rate

  up to 30th day after surgery

Study Arms (2)

CRT+concurrent PD-1 inhibition

EXPERIMENTAL

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)

CRT without PD-1 inhibition

ACTIVE COMPARATOR

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)

Interventions

Long-course chemoradiation, with Tislelizumab (PD-1 inhibitor) COMBINATION_PRODUCT

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.

CRT+concurrent PD-1 inhibition

Long-course chemoradiation, without Tislelizumab (PD-1 inhibitor) COMBINATION_PRODUCT

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.

CRT without PD-1 inhibition

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (1)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

RECRUITING

MeSH Terms

Interventions

Immune Checkpoint Inhibitors

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Zhang Zhongtao

  Beijing Friendship Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhang Zhongtao, MD

CONTACT

+8613801060364; zhangzht@ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Masking is not practically possible
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2023
• First Posted: May 6, 2023
• Study Start: October 1, 2022
• Primary Completion: November 1, 2024
• Study Completion: December 1, 2025
• Last Updated: May 6, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)