Neoadjuvant Chemoradiotherapy Combined With Tislelizumab in the Treatment of Locally Advanced Rectal Cancer

Neoadjuvant Chemoradiotherapy Combined With Tislelizumab in the Treatment of Locally Advanced Rectal Cancer--Randomized, Open, Multicenter Clinical Study

To compare the efficacy of Neoadjuvant Chemoradiotherapy Combined With/without Tislelizumab in the Treatment of Locally Advanced Rectal Cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Immunotherapy
• Intervention / Treatment: Drug: Capecitabine; Drug: oxaliplatin; Radiation: short-range radiotherapy; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yang Chun kang, Doctor of Medicine; Phone Number: 86 13509333116; Email: chuck330@163.com
• Study Contact Backup: Name: Wu Jun xin, Doctor of Medicine; Phone Number: 86 13635293859; Email: junxinwu@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18-75, male or female;
• Rectal adenocarcinoma confirmed by histopathology;
• The lower margin of the tumor as assessed by MRI was below peritoneal reflex-and cT3 was associated with one or more risk factors（cT3c-d，cN1-2；MRF+；EMVI+）;
• Patients who are expected to achieve R0 resection;
• Can swallow pills normally;
• ECOG PS 0-1;
• Have not received any previous anti-tumor therapy for rectal cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.;
• Surgical treatment is planned after completion of neoadjuvant therapy;
• No contraindications;
• Fertile female subjects shall have a negative serological pregnancy test within 72 hours prior to the start of trial drug administration and use effective contraceptive methods during the trial and for at least 3 months after the last dose;For male subjects with fertile female partners, effective contraceptive measures should be used during the trial period and for 3 months after the last dose;

Exclusion Criteria:

• Have a history of allergy to monoclonal antibody, tirelizumab, capecitabine, oxaliplatin or other platinum drugs;
• Have previously received or are currently receiving any of the following treatments:

A) any surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy for the tumor; B) being treated with an immunosuppressive drug or systemic hormone for immunosuppression purposes within 2 weeks prior to initial use of the study drug (dose >10mg/ day of prednisone or equivalent);In the absence of active autoimmune disease, inhaled or topical steroids and adrenocorticosteroid replacement at doses >10mg/ d of prednisone or equivalent are permitted; C) received live attenuated vaccine within 4 weeks prior to initial use of the study drug; D) major surgery or severe trauma within 4 weeks prior to first use of the study drug;

• Have any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy);Patients with complete remission of psoriasis or childhood asthma/allergy who do not require any intervention as adults may be considered for inclusion, but patients requiring medical intervention with bronchodilators may not be included;
• A history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, or a history of organ transplantation or allogeneic bone marrow transplantation;
• There is not a good control of the heart of the clinical symptoms or disease, including but not limited to: such as (1) the NYHA class II or above for heart failure, (2) the unstable angina, myocardial infarction occurred within 1 year (3), (4) have clinical significance on the chamber of sex or ventricular arrhythmias without clinical intervention or poorly controlled clinical intervention;
• Severe infection (CTCAE > level 2) occurred within 4 weeks prior to the first use of the study drug, such as severe pneumonia, bacteremia, and complications of infection requiring hospitalization;Baseline chest imaging suggests active lung inflammation, signs and symptoms of infection within 14 days prior to initial use of the study drug, or requiring oral or intravenous antibiotic treatment, except for prophylactic use of antibiotics;
• Those who were found to have active pulmonary tuberculosis infection through medical history or CT examination, or had active pulmonary tuberculosis infection history within 1 year before enrollment, or had active pulmonary tuberculosis infection history more than 1 year ago but without formal treatment;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV RNA higher than the detection limit of analysis method);
• Other malignancies diagnosed within 5 years prior to the first use of the study drug, unless malignancies with a low risk of metastasis or death (5-year survival >90%), such as adequately treated basal cell carcinoma of the skin or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, may be considered for inclusion;
• Pregnant or lactating women;
• In the investigator's judgment, there are other factors that may lead to forced termination of the study, such as other serious medical conditions (including mental illness) requiring concurrent treatment, alcoholism, drug abuse, family or social factors, and factors that may affect the safety or compliance of the subjects.

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: short-range radiotherapy sequential Tislelizumab combined with chemotherapy	Drug: Capecitabine; Participants will receive Capecitabine, 1000mg/m2, day 1-14 of every 3 weeks for 6 cycles; Drug: oxaliplatin; Participants will receive oxaliplatin, 130mg/m2, day 1 of every 3 weeks for 6 cycles.; Radiation: short-range radiotherapy; 5*5Gy，d1-d5; Drug: Tislelizumab; Participants will receive Tislelizumab, 200mg, intravenously over 30 - 60 minutes, day 1 of every 3 weeks for 6 cycles.
Experimental: short-range radiotherapy combined with chemotherapy	Drug: Capecitabine; Participants will receive Capecitabine, 1000mg/m2, day 1-14 of every 3 weeks for 6 cycles; Drug: oxaliplatin; Participants will receive oxaliplatin, 130mg/m2, day 1 of every 3 weeks for 6 cycles.; Radiation: short-range radiotherapy; 5*5Gy，d1-d5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate	Pathological examination of resected tissue samples revealed no residual tumor cells.	4 weeks after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response rate	The percentage of active tumor cells in excised tissue samples was less than 10%	4 weeks after surgery
overall survival	Defined from date of Signing ICF to date of first documentation of death from any cause or censored at the date of the last follow-up.	every 3 months (up to 36 months）

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Capecitabine; Oxaliplatin; Tislelizumab
• Other Study ID Numbers: TCO trial

Drug and device information, study documents

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