This prospective, single-center, randomized controlled trial aims to assessing the efficacy and safety of neoadjuvant chemoradiation plus Tislelizumab (PD-1 inhibitor) with or without Probio-M9 and subsequent TME surgery, by comparing assorted endpoints between two experiment groups (Experiment group 1: chemoradiation+PD-1 inhibitor+Probio-M9; Experiment group 2: chemoradiation+PD-1 inhibitor+placebo) with a control group (chemoradiation only).
Patients with clinically staged II-III pMMR/MSS locally advanced rectal adenocarcinoma (≤10 cm from anal verge) will receive long-course chemoradiotherapy (50 Gy/25 fractions) with concurrent Capecitabine, followed by two cycles of CapeOX chemotherapy and Tislelizumab (200 mg IV every 3 weeks). Participants will be randomized to receive either daily oral Probio-M9 (2 g) or matched placebo from treatment initiation until surgery.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Chemoradiation with PD-1 inhibitor (tislelizumab), with or without Probio-M9. Probio-M9 is administered orally at a dose of 2 g (one sachet) once daily. Treatment begins at the initiation of neoadjuvant chemoradiotherapy and continues until the day before surgical resection.
Chemoradiation with PD-1 inhibitor (tislelizumab) with placebo. Placebo is administered orally at a dose of 2 g (one sachet) once daily. Treatment begins at the initiation of neoadjuvant chemoradiotherapy and continues until the day before surgical resection.
Seventh Medical Center of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGpCR rate
pathological complete response rate
Time frame: within 10 days after surgery
2-y OS rate
2-year overall survival rate
Time frame: 2 year
2-y DFS rate
2-year disease free survival rate
Time frame: 2 year
3-y OS rate
3-year overall survival rate
Time frame: 3 year
3-y DFS rate
3-year disease free survival rate
Time frame: 3 year
5-y OS rate
5-year overall survival rate
Time frame: 5 year
5-y DFS rate
5-year disease free survival rate
Time frame: 5 year
immune-related adverse event rate
adverse event rate that is deemed to be associated with PD-1 inhibition
Time frame: from commencing of PD-1 inhibition to the 30th day after surgery
Changes in Gut Microbiota Composition
Gut microbiota composition will be analyzed using metagenomic sequencing of stool samples. Fecal samples will be collected to evaluate microbial diversity, relative abundance of bacterial taxa, and functional pathway alterations during neoadjuvant treatment.
Time frame: Stool samples will be collected at baseline (Day 1), Day 25 during treatment, and prior to surgery.
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