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

Official title

Short-Course Radiotherapy Followed by Liposomal Irinotecan, Oxaliplatin, Capecitabine, and Sintilimab as Total Neoadjuvant Therapy in High-Risk Locally Advanced Rectal Cancer: A Single-Arm, Single-Center, Exploratory Study

Overview

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.

Interventions

• Radiation SCRT
  25 Gy / 5 F
• Drug Liposomal Irinotecan
  50 mg/m², intravenously (IV) on Day 1 of each cycle.
• Drug Oxaliplatin
  85 mg/m², IV on Day 1 of each cycle.
• Drug Capecitabine
  800 mg/m², orally twice daily from Day 1 to Day 14 of each cycle.
• Drug Sintilimab
  200 mg, IV on Day 1 of each cycle.

Primary outcome measures

• Complete Response Rate [Time frame: 6 months]

Secondary outcome measures (8)

• Major Pathological Response (MPR) Rate [Time frame: 6 months]
• Objective Response Rate (ORR) [Time frame: 6 months]
• Disease Control Rate (DCR) [Time frame: 6 months]
• Progression-Free Survival (PFS) [Time frame: 3 years]
• Overall Survival (OS) [Time frame: 5 years]
• 3-Year Event-Free Survival (3y-EFS) Rate [Time frame: 3 years]
• 3-Year Disease-Free Survival (3y-DFS) Rate [Time frame: 3 years]
• Incidence of Adverse Events (AEs) [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Other Exclusionary Conditions: Any other acute or chronic disease, mental disorder, or laboratory abnormality that, in the investigator's judgment, may increase the risk associated with study participation or drug administration, or interfere with the interpretation of study results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Hongli Liu — Wuhan

Identifiers

NCT: NCT07474103 · WUGO-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗