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

NCT07104604 | Recruiting Phase 2

• 1 other identifier: CancerShantouUMC 2
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 2

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.

Conditions

Rectal Cancer

Keywords

Neoadjuvant therapy; rectal cancer; liposomal irinotecan; radiotherapy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Complete 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.

  At surgery, or at the confirmatory organ-preservation assessment approximately 12-16 weeks after the start of neoadjuvant therapy.

Secondary Outcomes (8)

• Major pathological response (MPR) rate

  At surgery

• Sphincter-preservation rate

  At surgery

• R0 resection rate

  At surgery

• Disease-free survival (DFS)

  Up to 24 months

• Local-regrowth-free survival and TME-free survival (watch-and-wait subgroup)

  Up to 24 months

Study Arms (1)

Liposomal Irinotecan

EXPERIMENTAL

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.

Drug: Liposomal Irinotecan+Tislelizumab+Capecitabine+Rradiotherapy

Interventions

Liposomal Irinotecan+Tislelizumab+Capecitabine+Rradiotherapy DRUG

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.

Also known as: New Neoadjuvant Treatment Approach

Liposomal Irinotecan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Affiliated Cancer Hospital of Shantou University Medical College: lead

Study Sites (2)

Shantou University Medical College Cancer Hospital

Shantou, Guangdong, 515000, China

RECRUITING

The First Affiliated Hospital of Shantou University Medical College

Shantou, Guangdong, 515041, China

NOT YET RECRUITING

Related Publications (5)

• Bang YJ, Li CP, Lee KH, Chiu CF, Park JO, Shan YS, Kim JS, Chen JS, Shim HJ, Rau KM, Choi HJ, Oh DY, Belanger B, Chen LT. Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study. Cancer Sci. 2020 Feb;111(2):513-527. doi: 10.1111/cas.14264. Epub 2019 Dec 20.

  PMID: 31789476 BACKGROUND

• Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-557. doi: 10.1016/S0140-6736(15)00986-1. Epub 2015 Nov 29.

  PMID: 26615328 BACKGROUND

• Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. doi: 10.1200/JCO.20.01932. Epub 2020 Oct 29.

  PMID: 33119477 BACKGROUND

• Yang Z, Gao J, Zheng J, Han J, Li A, Liu G, Sun Y, Zhang J, Chen G, Xu R, Zhang X, Liu Y, Bai Z, Deng W, He W, Yao H, Zhang Z. Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer (NECTAR): a multi-center phase 2 study. Signal Transduct Target Ther. 2024 Mar 11;9(1):56. doi: 10.1038/s41392-024-01762-y.

  PMID: 38462629 BACKGROUND

• Rahma OE, Yothers G, Hong TS, Russell MM, You YN, Parker W, Jacobs SA, Colangelo LH, Lucas PC, Gollub MJ, Hall WA, Kachnic LA, Vijayvergia N, O'Rourke MA, Faller BA, Valicenti RK, Schefter TE, George S, Kainthla R, Stella PJ, Sigurdson E, Wolmark N, George TJ. Use of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Initial Results From the Pembrolizumab Arm of a Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Aug 1;7(8):1225-1230. doi: 10.1001/jamaoncol.2021.1683.

  PMID: 34196693 BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Jiarui Lin

CONTACT

86-13794112671; zljr@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor，Doctor

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: August 5, 2025
• Study Start: October 20, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: July 24, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)