Rectal Cancer
Conditions
Keywords
Neoadjuvant therapy, rectal cancer, liposomal irinotecan, radiotherapy, immunotherapy
Brief summary
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.
Interventions
DRUGLiposomal Irinotecan+Tislelizumab+Capecitabine+Rradiotherapy
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.
Sponsors
Affiliated Cancer Hospital of Shantou University Medical College
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Here is the updated format for the \*\*Eligibility Criteria\*\* with bullet points for each item: Inclusion Criteria: * Age: 18-75 years, no gender restriction * ECOG score 0-1 * Biopsy-confirmed pMMR (proficient mismatch repair) localized advanced low rectal adenocarcinoma (tumor's lower edge ≤ 10 cm from the anus) * Presence of the following high-risk factors: T3N+/T4/N2/EMVI+/MRF+/lateral lymph node metastasis/inability to undergo sphincter-preserving surgery * Routine chest and abdominal CT scans showing no distant metastasis * Bone marrow function: Neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count (PLT) ≥ 100 × 10\^9/L, hemoglobin (Hb) ≥ 70 g/L * Liver function: ALT, AST ≤ 2.5 × ULN (upper limit of normal); total bilirubin ≤ 1.5 × ULN; serum albumin ≥ 3 g/dL * Kidney function: Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance ≥ 60 ml/min (calculated using the Cockcroft-Gault formula) * For females and patients with reproductive potential, a negative pregnancy test must be done within 72 hours before starting the treatment, and the patient must agree to avoid pregnancy during the study treatment and for 6 months after the treatment. For males with reproductive potential partners, the patient must agree to use adequate medically approved contraception during and for 90 days after the final study treatment * Patients must agree to receive the study's neoadjuvant chemotherapy regimen and sign an informed consent form
Exclusion criteria
* Patients with a history of other malignancies within the past 5 years (except for cured and non-recurring cancers such as in situ carcinoma, basal cell carcinoma of the skin, etc.) * Patients with active, uncontrolled bacterial, viral, or fungal infections requiring systemic treatment, defined by persistent signs/symptoms related to infection, which do not improve despite appropriate antibiotics, antiviral treatments, and/or other therapies * Patients with uncontrolled systemic diseases, including unstable angina, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmia, history of severe pericardial disease, or other cardiovascular diseases; uncontrolled hypertension (defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg despite appropriate antihypertensive treatment), or a history of hypertensive crisis, hypertensive encephalopathy; uncontrolled diabetes (fasting blood glucose ≥ 10 mmol/L), etc. * Patients known to be allergic or intolerant to the treatment drugs or excipients used in this study * Any clinical indicators showing contraindications to chemotherapy and surgery * Patients using strong inhibitors or inducers of enzymes such as CYP3A4, CYP2C8, and UGT1A1 * Pregnant or breastfeeding women, and female patients of reproductive potential who refuse to use appropriate contraceptive measures during the study * Patients who participated in other clinical trials within 4 weeks before enrollment * Patients whom the investigator deems unsuitable for participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR) rate | At surgery, or at the confirmatory organ-preservation assessment approximately 12-16 weeks after the start of neoadjuvant therapy. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major pathological response (MPR) rate | At surgery | 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). |
| Sphincter-preservation rate | At surgery | The proportion of resected participants who undergo sphincter-preserving surgery. |
| R0 resection rate | At surgery | The proportion of resected participants achieving an R0 resection, defined as no tumour cells within 1 mm of the resection margin. |
| Disease-free survival (DFS) | Up to 24 months | 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. |
| Local-regrowth-free survival and TME-free survival (watch-and-wait subgroup) | Up to 24 months | 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). |
| Anorectal function (LARS score) | 3, 6, and 12 months after stoma reversal (resected) or after confirmed cCR (watch-and-wait) | Anorectal function assessed using the validated Low Anterior Resection Syndrome (LARS) score. |
| Adverse events (safety and tolerability) | From first dose until 28 days after the last dose | 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. |
| Treatment feasibility (regimen completion and dose intensity) | From first dose to completion of neoadjuvant therapy (approximately 12-16 weeks) | 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. |
Countries
China
Contacts
CONTACTJiarui Lin
Outcome results
None listed