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

Phase 2

Recruiting

• Conditions: Locally Advanced Rectal Cancer
• Interventions: Combination Product: Long-course chemoradiation, without Tislelizumab (PD-1 inhibitor); Combination Product: Long-course chemoradiation, with Tislelizumab (PD-1 inhibitor)

• Registration Number: NCT05845268
• Lead Sponsor: Beijing Friendship Hospital

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).

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 Timeline

• Status Verified: 2022-10
• Study Start: 2022-10-01
• Study First Submitted: 2023-03-30
• Study First Submitted QC: 2023-04-25
• Last Update Submitted: 2023-04-25
• Study First Posted: 2023-05-06
• Last Update Posted: 2023-05-06
• Primary Completion: 2024-11-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 102

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CRT without PD-1 inhibition	Long-course chemoradiation, without Tislelizumab (PD-1 inhibitor)	Long-course chemoradiation plus PD-1 inhibition with no PD-1 inhibition. TME surgery is scheduled in 10\~13 weeks after completion of radiation.
CRT+concurrent PD-1 inhibition	Long-course chemoradiation, with Tislelizumab (PD-1 inhibitor)	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.

Primary Outcome Measures

Name	Time	Method
pCR rate	within 10 days after surgery	pathological complete response rate
cCR rate	12-13 weeks after radiotherapy ends	clinical complete response rate

Secondary Outcome Measures

Name	Time	Method
ORR	within 10 days after surgery	objective response rate
immune-related adverse event rate	up to 30th day after surgery	adverse event rate that is deemed to be associated with PD-1 inhibition
NAR score	within 10 days after surgery	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.
OPR	immediately after surgery	organ preservation rate

Trial Locations

Locations (1)

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China