Immunotherapy, Neoadjuvant Therapy, Probio-M9, Randomized, Rectal Cancer, Adenocarcinoma, Tislelizumab
Conditions
Keywords
Probio-M9, tislelizumab, locally advanced rectal cancer
Brief summary
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).
Detailed description
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.
Interventions
COMBINATION_PRODUCTCRT+PD-1 inhibitor+Probio-M9
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.
COMBINATION_PRODUCTCRT+PD-1 inhibitor+placebo
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.
Sponsors
Seventh Medical Center of PLA General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * ECOG performance status 0-2 * Biopsy-proven rectal adenocarcinoma * Distal tumor margin within 10 cm of the anal verge * No distant metastasis * Clinical stage II or III based on MRI (T4b excluded) * Maximum diameter of rectal tumor ≥ 10 mm on baseline CT or MRI (measurable lesion according to RECIST 1.1) * Willing and able to comply with the study protocol * Willing to provide blood and tissue specimens for research purposes * No prior anti-tumor treatment (e.g., radiotherapy, chemotherapy, immunotherapy, biological therapy, or herbal therapy) * No history of immune system disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, autoimmune hemolytic anemia, thyroid autoimmune disease, ulcerative colitis, HIV infection, etc.) * No significant dysfunction of major organs (heart, lung, liver, kidney) * No jaundice or gastrointestinal obstruction * No acute or ongoing infection * Adequate hematologic and biochemical function including: * Neutrophils ≥ 1.5 × 10\^9/L * Hemoglobin ≥ 80 g/L * Platelets ≥ 100 × 10\^9/L * Serum creatinine ≤ 1.5 × ULN * Total bilirubin ≤ 1.5 × ULN * ALT and AST ≤ 2.5 × ULN * No social or psychiatric disorders that may interfere with study participation * Women of childbearing potential must have a negative pregnancy test before enrollment and must use effective contraception from study entry until 60 days after the last dose of study drug
Exclusion criteria
* History of multiple primary cancers or concomitant malignant tumors other than rectal cancer * Receipt of any anti-cancer treatment (e.g., surgery, chemotherapy, radiotherapy, or other systemic therapies) within the past 5 years * History of recent major surgery * Conditions that may affect the gastrointestinal absorption of capecitabine (e.g., inability to swallow, persistent nausea or vomiting, chronic diarrhea) * Uncontrolled or severe concomitant diseases of any kind * Known allergy or hypersensitivity to any components of the study drugs * Estimated life expectancy ≤ 5 years due to any cause * Planned or prior organ or bone marrow transplantation * Use of immunosuppressive therapy or systemic corticosteroids for immunosuppressive purposes within 1 month prior to enrollment * History of central nervous system disorders that may impair the ability to provide informed consent or affect compliance with oral medication (investigator discretion) * Other conditions that may interfere with study results or lead to premature discontinuation of study treatment (e.g., alcoholism or drug abuse) * Pregnant or breastfeeding women, or women planning to become pregnant during the treatment period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR rate | within 10 days after surgery | pathological complete response rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-y OS rate | 2 year | 2-year overall survival rate |
| 2-y DFS rate | 2 year | 2-year disease free survival rate |
| 3-y OS rate | 3 year | 3-year overall survival rate |
| 3-y DFS rate | 3 year | 3-year disease free survival rate |
| 5-y OS rate | 5 year | 5-year overall survival rate |
| 5-y DFS rate | 5 year | 5-year disease free survival rate |
| immune-related adverse event rate | from commencing of PD-1 inhibition to the 30th day after surgery | adverse event rate that is deemed to be associated with PD-1 inhibition |
| Changes in Gut Microbiota Composition | Stool samples will be collected at baseline (Day 1), Day 25 during treatment, and prior to surgery. | 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. |
Countries
China
Contacts
CONTACTJunfeng Du, PhD
Outcome results
None listed