Preoperative Chemoradiotherapy Combined With Consolidation or Induction NALIRIFOX in Rectal Cancer.

The Efficacy and Safety of Long-Course Preoperative Chemoradiotherapy Combined With Consolidation or Induction NALIRIFOX Chemotherapy in the Treatment of Locally Advanced Rectal Cancer: A Prospective, Multicenter, Phase II Study.

The Efficacy and Safety of Long-Course Preoperative Chemoradiotherapy Combined with Consolidation or Induction NALIRIFOX Chemotherapy in the Treatment of Locally Advanced Rectal Cancer: A Prospective, Multicenter, Phase II Study.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Radiation: Concurrent Chemoradiotherapy（Radiation + Capecitabine）; Drug: irinotecan hydrochloride liposome injection; Drug: Oxaliplatin; Drug: 5-FU

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yongheng Li, MD; Phone Number: 13810277398; Email: yonghenglee@163.com
• Study Contact Backup: Name: Xicheng Wang, MD; Phone Number: 13439563949

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Contact: Yongheng Li, MD; Phone Number: 13810277398; Email: yonghenglee@163.com
    • Contact: Xicheng Wang, MD; Phone Number: 13439563949

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects participate in the study need to sign the informed consent, and demonstrate good compliance.
2. Age: 18~75 years old.
3. Histopathologically confirmed rectal adenocarcinoma.
4. Locally advanced rectal cancer, determined at baseline.
5. No prior systemic therapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0~1.
7. Expected survival ≥ 12 months.

8. Adequate bone marrow function (In the absence of blood transfusion within 14 days, correction with granulocyte colony-stimulating factor or other hematopoietic stimulating factor was not used within 7 days prior to laboratory examination) :

   ①Absolute neutrophil count (ANC) ≥1.5×10^9/L, Platelet count ≥100×10^9/L, Hemoglobin (Hb) ≥9g/dL.

   ② Liver function: Total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN, liver metastasis, AST and ALT≤5×ULN.

   ③ Renal function: Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min.

   ④International Normalized Ratio (INR) ≤ 1.5 ULN, Prothrombin time and activated partial thromboplastin time (APTT) ≤ 1.5 ULN

9. Microsatellite Stability (MSS) or proficient MisMatch Repair (pMMR).

Exclusion Criteria:

1. Within 4 weeks prior to treatment, subjects must not have received radiotherapy, surgery, chemotherapy, immunotherapy for tumors, molecular targeted therapies, or other investigational drugs.
2. microsatellite instability (MSI) or mismatch repair gene deletion (dMMR)
3. Distant metastasis
4. Significant clinical bleeding symptoms or significant bleeding tendency within 3 months prior to treatment (bleeding > 30ml within 3 months), hematemesis, black stool, blood in the stool), hemoptysis (> 5 mL of fresh blood within 4 weeks), etc. Treatment of venous/venous thrombotic events within the first 6 months, such as cerebrovascular accidents (including transient brain lesions) Ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; Or need to use warfarin or Long-term anticoagulant therapy with heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or chlorine) is required Picogrel ≥75 mg/day).
5. During screening, tumors were found to invade large vascular structures, such as pulmonary artery, superior vena cava or inferior vena cava that there was a risk of major bleeding by the investigator judged.
6. Active heart disease, including myocardial infarction, severe/unstable angina, occurred 6 months before treatment. ultrasonic Left ventricular ejection fraction <50% was detected by cardiogram, indicating poor arrhythmia control.
7. High blood pressure that is not well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg).
8. Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc.
9. Known or suspected allergy to the investigational drug or a similar drug.
10. Active or uncontrolled severe infection.
11. Known human immunodeficiency virus (HIV) infection.
12. Any other disease with clinically significant metabolic abnormalities, physical abnormalities, or laboratory abnormalities Often, in the investigator's judgment, there is reason to suspect that the patient has a disease or condition that is not suitable for use of the investigational drug state (such as having a seizure and requiring treatment) that will either affect the interpretation of the study results or make the patient In a high-risk situation.
13. Patients who have been co-administered a potent CYP3A4 inducer within 3 weeks prior to first dosing, or a potent CYP3A4 inhibitor or a potent UGT1A1 inhibitor within 3 weeks prior to first dosing
14. Inability to comply with study protocols or study procedures.
15. Patients who are not suitable to participate in this trial judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Long-Course Preoperative Chemoradiotherapy Combined with Consolidation NALIRIFOX Chemotherapy; Patients will receive Concurrent Chemoradiotherapy（Radiation + Capecitabine） followed by NALIRIFOX Concurrent Chemoradiotherapy：5 Weeks in total NALIRIFOX：8 Weeks in total	Radiation: Concurrent Chemoradiotherapy（Radiation + Capecitabine）; Capecitabine 825 mg/m^2 Po BlD, Monday-Friday, on days of radiation treatment only, throughout the duration of RT Radiation：45-50Gy/25fractions/5 weeks，5fractions/week; Drug: irinotecan hydrochloride liposome injection; Irinotecan hydrochloride liposome injection (50mg/m^2) will be administered by intravenous infusion on day 1 in a 2-week treatment cycle.; Other Names: Nal-IRI; Drug: Oxaliplatin; Oxaliplatin (60mg/m^2) will be administered by intravenous infusion on day 1 in a 2-week treatment cycle.; Other Names: OXA; Drug: 5-FU; 5-FU (2400mg/m^2) will be administered by intravenous infusion on 46h in a 2-week treatment cycle.; Other Names: fluorouracil
Experimental: Long-Course Preoperative Chemoradiotherapy Combined with Induction NALIRIFOX Chemotherapy; Patients will receive NALIRIFOX followed by Concurrent Chemoradiotherapy（Radiation + Capecitabine） Concurrent Chemoradiotherapy：5 Weeks in total NALIRIFOX：8 Weeks in total	Radiation: Concurrent Chemoradiotherapy（Radiation + Capecitabine）; Capecitabine 825 mg/m^2 Po BlD, Monday-Friday, on days of radiation treatment only, throughout the duration of RT Radiation：45-50Gy/25fractions/5 weeks，5fractions/week; Drug: irinotecan hydrochloride liposome injection; Irinotecan hydrochloride liposome injection (50mg/m^2) will be administered by intravenous infusion on day 1 in a 2-week treatment cycle.; Other Names: Nal-IRI; Drug: Oxaliplatin; Oxaliplatin (60mg/m^2) will be administered by intravenous infusion on day 1 in a 2-week treatment cycle.; Other Names: OXA; Drug: 5-FU; 5-FU (2400mg/m^2) will be administered by intravenous infusion on 46h in a 2-week treatment cycle.; Other Names: fluorouracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate	To evaluate the efficacy of anti-tumor	From baseline up to approximately 3 months

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Collaborators: CSPC Ouyi Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Yongheng Li, MD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: March 12, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Capecitabine; Oxaliplatin; Irinotecan; Fluorouracil
• Other Study ID Numbers: CSPC-DNY- LARC-BJ01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No