SCRT-NALIRIXELOX+Sintilimab as TNT for High-Risk LARC

NCT07474103 | Recruiting

• 1 other identifier: WUGO-003
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, exploratory clinical study for patients with newly diagnosed, high-risk, locally advanced rectal cancer. The study aims to evaluate the effectiveness and safety of a comprehensive pre-surgery (neoadjuvant) treatment strategy. All participants will receive a short course of radiation therapy (25 Gy in 5 fractions) over one week. This will be followed by a combination of chemotherapy (Liposomal Irinotecan, Oxaliplatin, and Capecitabine) and immunotherapy (Sintilimab). This combined treatment is administered for six cycles. For patients who achieve a complete response, the option to avoid immediate surgery and enter a close monitoring program ("Watch and Wait") will be considered.

Conditions

Rectal Cancer, Adenocarcinoma

Keywords

total neoadjuvant therapy; Short-Course Radiotherapy; Liposomal Irinotecan; rectal cancer

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  The proportion of participants achieving either a Pathologic Complete Response (pCR) or a Clinical Complete Response (cCR). pCR is defined as the absence of viable tumor cells in the primary tumor and lymph nodes (ypT0N0) upon pathological examination after surgery. cCR is defined as the absence of residual tumor as confirmed by imaging (MRI/PET-CT) and clinical assessment (e.g., digital rectal exam, endoscopy) in patients who forgo immediate surgery.

  6 months

Secondary Outcomes (8)

• Major Pathological Response (MPR) Rate

  6 months

• Objective Response Rate (ORR)

  6 months

• Disease Control Rate (DCR)

  6 months

• Progression-Free Survival (PFS)

  3 years

• Overall Survival (OS)

  5 years

Study Arms (1)

SCRT followed by NALIRIXELOX + Sintilimab

EXPERIMENTAL

1. Short-Course Radiotherapy (SCRT) 2. Systemic Therapy (Chemotherapy + Immunotherapy): Liposomal Irinotecan+Oxaliplatin+Capecitabine+Sintilimab

Radiation: SCRT; Drug: Liposomal Irinotecan; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Sintilimab

Interventions

SCRT RADIATION

25 Gy / 5 F

Also known as: Short-Course Radiotherapy

SCRT followed by NALIRIXELOX + Sintilimab

Liposomal Irinotecan DRUG

50 mg/m², intravenously (IV) on Day 1 of each cycle.

Also known as: Nal-IRI, irinotecan liposome

SCRT followed by NALIRIXELOX + Sintilimab

Oxaliplatin DRUG

85 mg/m², IV on Day 1 of each cycle.

Also known as: OX

SCRT followed by NALIRIXELOX + Sintilimab

Capecitabine DRUG

800 mg/m², orally twice daily from Day 1 to Day 14 of each cycle.

Also known as: Xeloda

SCRT followed by NALIRIXELOX + Sintilimab

Sintilimab DRUG

200 mg, IV on Day 1 of each cycle.

Also known as: IBI308

SCRT followed by NALIRIXELOX + Sintilimab

Eligibility Criteria

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

You may qualify if:

• Voluntary Participation: Subjects voluntarily participate in the study, sign the informed consent form, and have good compliance.
• Age and Gender: Age between 18 and 75 years, any gender.
• Pathological Diagnosis: Histologically or cytologically confirmed rectal adenocarcinoma; confirmed mismatch repair proficient (pMMR) or microsatellite stable (MSS) by genetic testing or immunohistochemistry.
• Disease Stage: Assessed as high-risk, mid-low (distance from the anal verge ≤10 cm) locally advanced rectal cancer by colonoscopy, digital rectal exam, or MRI. High-risk definition: Meeting at least one of the following: cT4, extramural vascular invasion (EMVI), tumor deposits, involvement of the mesorectal fascia or intersphincteric plane.
• Prior Treatment: No prior anti-tumor therapy for this rectal cancer (including surgery, radiotherapy, chemotherapy, immunotherapy, or targeted therapy).
• Measurable Lesion: At least one measurable lesion according to RECIST v1.1 criteria.
• Tumor Tissue Sample: Must provide tumor tissue samples for biomarker analysis.
• Adequate Organ Function (within 7 days before the first dose): 1) Hematological: Hemoglobin ≥90 g/L; White Blood Cell count ≥3.0 x 10⁹/L; Absolute Neutrophil Count ≥1.5 x 10⁹/L; Platelets ≥100 x 10⁹/L. 2) Hepatic: Total Bilirubin \<1.5 x ULN; AST and ALT ≤2.5 x ULN; Albumin ≥30 g/L. 3) Renal: Serum Creatinine ≤1.5 x ULN OR Creatinine Clearance ≥50 mL/min. 4) Coagulation: INR ≤1.5 x ULN (or ≤3 x ULN if on stable anticoagulant therapy); PTT or aPTT ≤1.5 x ULN (or ≤3 x ULN if on stable anticoagulant therapy).
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life Expectancy: Expected survival time ≥3 months.
• Good organ function.
• Contraception: Subjects of childbearing potential must agree to use effective contraception during the treatment period and for 6 months after the last dose.

You may not qualify if:

• Other Malignancies: Diagnosis of another malignancy within 5 years prior to the first dose, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma in situ, localized prostate cancer, or papillary thyroid cancer, etc.
• Allergy: Known or suspected allergy to the study drugs or any of their excipients.
• Pregnancy and Lactation: Pregnant or lactating women, or women planning to become pregnant during the study or within 6 months after the last dose.
• Central Nervous System Disease: Known active epilepsy, active central nervous system (CNS) metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
• Significant Cardiovascular Disease: Clinically significant uncontrolled cardiovascular disease.
• History of Allergic Disease: History of allergic diathesis, asthma, or atopic dermatitis.
• Pleural Effusion/Ascites: Presence of significant pleural effusion or ascites.
• Active Autoimmune Disease: Active autoimmune disease requiring systemic treatment within 2 years prior to the first dose (replacement therapy is allowed).
• Immunosuppressant Use: Use of systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressants within 2 weeks prior to enrollment.
• Interstitial Lung Disease: History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or evidence of active pneumonia on screening chest CT scan.
• Transplantation History: History of allogeneic organ transplantation or hematopoietic stem cell transplantation.
• Active Infection: Positive HIV test result; Active Hepatitis B (HBV DNA ≥10⁴ copies/mL); Active Hepatitis C (HCV RNA ≥10³ copies/mL); Active Tuberculosis.
• Gastrointestinal Risk: History of bowel obstruction within 28 days prior to the first study dose; High risk of gastrointestinal perforation.
• Recent Major Surgery: Major surgical procedure within 4 weeks prior to enrollment.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Hongli Liu

Wuhan, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

irinotecan sucrosofate; Oxaliplatin; Capecitabine; sintilimab

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Hongli Liu, Professor

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hongli Liu, Professor

CONTACT

13995680822; hongli_liu@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 16, 2026
• Study Start: November 30, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 16, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)