Study on the Efficacy and Safety of Neoadjuvant Radiotherapy Combined With Toripalimab, Liposomal Irinotecan, and Capecitabine in the Treatment of pMMR Locally Advanced Rectal Adenocarcinoma With Low Rectal Involvement

Shantou University Medical College

Status and phase: Enrolling; Phase 1

Conditions: Rectal Cancer

Treatments: Drug: Liposomal Irinotecan

Study type: Interventional

Funder types: Other

Identifiers

NCT07104604

CancerShantouUMC 2

Details and patient eligibility

About

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.

Enrollment: 59 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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59 participants in 1 patient group

Liposomal Irinotecan

Experimental group

Description:

Treatment regimen: 1. During radiotherapy: Radiotherapy 50Gy/25F + liposomal irinotecan 30mg/m² ivgtt qw w1-w4 + capecitabine 625mg/m² Bid, orally on radiotherapy days + tislelizumab 200mg ivgtt q3w; 2. Radiotherapy-surgery interval: Liposomal irinotecan 70mg/m² ivgtt q3w + capecitabine 1000mg/m² Bid D1-D14 q3w + tislelizumab 200mg ivgtt q3w.

Treatment:

Drug: Liposomal Irinotecan