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

Official title

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.

Overview

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.

Interventions

• 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.
• Drug Oxaliplatin
  Oxaliplatin (60mg/m\^2) will be administered by intravenous infusion on day 1 in a 2-week treatment cycle.
• Drug 5-FU
  5-FU (2400mg/m\^2) will be administered by intravenous infusion on 46h in a 2-week treatment cycle.

Primary outcome measures

• Pathological complete response rate [Time frame: From baseline up to approximately 3 months]

Eligibility criteria

Inclusion criteria

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

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

Exclusion criteria

• Within 4 weeks prior to treatment, subjects must not have received radiotherapy, surgery, chemotherapy, immunotherapy for tumors, molecular targeted therapies, or other investigational drugs.
• microsatellite instability (MSI) or mismatch repair gene deletion (dMMR)
• Distant metastasis
• 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).
• 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.
• 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.
• High blood pressure that is not well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg).
• Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc.
• Known or suspected allergy to the investigational drug or a similar drug.
• Active or uncontrolled severe infection.
• Known human immunodeficiency virus (HIV) infection.
• 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.
• 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
• Inability to comply with study protocols or study procedures.
• Patients who are not suitable to participate in this trial judged by the investigator.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT06894797 · CSPC-DNY- LARC-BJ01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗