The goal of this clinical trial is to evaluating the efficacy and safety of radiotherapy combined with Tislelizumab, Liposomal Irinotecan, and Capecitabine in patients with locally advanced mid-lower rectal cancer with pMMR.. Patients would be included as:1. Aged between 18-75 years, with no gender restrictions; 2. Biopsy pathology confirmed as pMMR type locally advanced mid-lower rectal adenocarcinoma (tumor lower margin ≤ 10 cm from the anal verge); 3.With the following high-risk factors: T3N+/T4/N2/EMVI+/MRF+/lateral lymph node metastasis/inability to preserve anal function during surgery; 4. No distant metastasis observed in routine chest and abdominal CT scans.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
In this study, the novel drug liposomal irinotecan was added, replacing the conventional formulation of irinotecan, and used as an intensified chemotherapy regimen (liposomal irinotecan + capecitabine) combined with immunotherapy and radiotherapy for neoadjuvant treatment of mid-lower rectal cancer.
Shantou University Medical College Cancer Hospital
Shantou, Guangdong, China
RECRUITINGThe First Affiliated Hospital of Shantou University Medical College
Shantou, Guangdong, China
NOT_YET_RECRUITINGComplete response (CR) rate
The complete response (CR) rate is defined as the proportion of all evaluable participants who achieve either a pathological complete response (pCR) or a clinical complete response (cCR). A participant is classified as a responder if they achieve pCR (defined as no residual tumour on postoperative pathology, ypT0N0) for patients undergoing surgical resection, or confirmed cCR (defined as no clinical, endoscopic, or radiological evidence of residual tumour) for patients managed with organ preservation without resection. These two response categories are mutually exclusive, and the CR rate is calculated using a single shared denominator consisting of all evaluable participants.
Time frame: At surgery, or at the confirmatory organ-preservation assessment approximately 12-16 weeks after the start of neoadjuvant therapy.
Major pathological response (MPR) rate
The major pathological response (MPR) rate is defined as the proportion of resected participants with 10% or fewer residual viable tumour cells in the resection specimen (i.e., at least 90% of the tumour eliminated).
Time frame: At surgery
Sphincter-preservation rate
The proportion of resected participants who undergo sphincter-preserving surgery.
Time frame: At surgery
R0 resection rate
The proportion of resected participants achieving an R0 resection, defined as no tumour cells within 1 mm of the resection margin.
Time frame: At surgery
Disease-free survival (DFS)
For resected participants, disease-free survival (DFS) is defined as the time from surgery to tumour recurrence or death from any cause; for watch-and-wait participants, DFS is defined as the time from the date of confirmed cCR to local regrowth, distant metastasis, or death from any cause (local regrowth is counted as a DFS event). A supportive analysis of DFS measured from the start of neoadjuvant therapy will also be reported to provide a common time origin across both treatment pathways. Participants without an event will be censored at the last tumour assessment.
Time frame: Up to 24 months
Local-regrowth-free survival and TME-free survival (watch-and-wait subgroup)
Among participants managed by organ preservation, two endpoints will be reported separately to distinguish salvageable local regrowth from oncological failure: local-regrowth-free survival (time from confirmed cCR to local regrowth) and TME-free survival (time from confirmed cCR to any total mesorectal excision, performed either for regrowth or by patient choice).
Time frame: Up to 24 months
Anorectal function (LARS score)
Anorectal function assessed using the validated Low Anterior Resection Syndrome (LARS) score.
Time frame: 3, 6, and 12 months after stoma reversal (resected) or after confirmed cCR (watch-and-wait)
Adverse events (safety and tolerability)
Adverse events assessed systematically and graded according to NCI-CTCAE v5.0, including overall adverse-event rate, grade 3 or higher adverse-event rate, chemotherapy-related and immune-related adverse-event rates, and serious adverse-event rate.
Time frame: From first dose until 28 days after the last dose
Treatment feasibility (regimen completion and dose intensity)
Feasibility of the four-modality neoadjuvant regimen, assessed by the proportion of participants completing the planned neoadjuvant treatment and by the relative dose intensity of each systemic agent (tislelizumab, liposomal irinotecan, and capecitabine) and of radiotherapy.
Time frame: From first dose to completion of neoadjuvant therapy (approximately 12-16 weeks)
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