Dietary Arginine Deprivation Combined With Chemoradiotherapy for Neoadjuvant Treatment of Rectal Cancer: A Randomized Controlled Trial

Inclusion Criteria:

• Signed written informed consent prior to any study-related procedures.
• Male or female, aged 18 to 80 years.
• Locally advanced mid-low rectal cancer staged as cT3, cT4, or node-positive by rectal MRI.
• ECOG performance status 0-1.
• NRS-2002 score \< 3.
• BMI ≥ 18.5 kg/m² (may be adjusted based on actual conditions).
• Able to take food orally or via feeding tube and tolerate enteral nutrition.
• Adequate organ function as defined by the following laboratory criteria:

1. ANC ≥ 1.5 × 10⁹/L (no G-CSF within 14 days);

2. Platelet count ≥ 100 × 10⁹/L;

3. Hemoglobin ≥ 9 g/dL (no transfusion or erythropoietin within 7 days);

4. Serum albumin ≥ 3.0 g/dL;

5. Total bilirubin ≤ 1.5 × ULN;

6. AST/ALT ≤ 2.5 × ULN;

7. Creatinine clearance ≥ 50 mL/min or serum creatinine ≤ 1.5 × ULN;

8. INR ≤ 1.5 × ULN, PT and APTT ≤ 1.5 × ULN;

9. Urine protein \< 2+ (if ≥ 2+, 24-hour urine protein \< 2.0 g allowed);

10. Cardiac enzyme profile within normal limits.

• Women of childbearing potential must agree to use reliable contraception from signing informed consent to at least 6 months after the last dose, with a negative serum HCG test within 3 days before treatment and non-lactating status.
• All participants at risk of pregnancy must use contraceptive methods with a failure rate of \< 1% per year throughout treatment until 120 days after the last study drug dose (or 180 days after the last chemotherapy).

Exclusion Criteria:

• Stage I or IV rectal cancer.
• Cognitive impairment or psychiatric disorders that interfere with understanding the study content.
• Central nervous system or meningeal metastases.
• Clinically symptomatic moderate or severe ascites (requiring therapeutic paracentesis within 2 weeks before starting study treatment; patients with minimal asymptomatic ascites on imaging may be enrolled).
• Uncontrolled or moderate to severe pleural effusion and pericardial effusion.
• Severe diarrhea, intractable vomiting, severe malabsorption syndrome, paralytic or mechanical intestinal obstruction; tracheoesophageal fistula, gastrointestinal perforation or fistula, or intra-abdominal abscess; gastrointestinal bleeding with CTCAE grade ≥ 3 within 6 months or CTCAE grade ≥ 2 within 3 months before study treatment.
• Other factors that may affect study results or cause forced termination (as judged by the investigator), such as alcoholism, drug abuse, other serious diseases requiring combined treatment (including psychiatric disorders), severe laboratory abnormalities, family or social factors, and other conditions that may affect patient safety or study data collection.
• Known allergy to active ingredients or excipients of the study drug or nutritional powder.
• Poorly controlled diabetes mellitus.
• Severe cardiovascular and cerebrovascular diseases, including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction, and major vascular diseases within 6 months before enrollment; poorly controlled symptomatic cardiac diseases, such as unstable angina, NYHA class ≥ II heart failure, LVEF \< 50% on echocardiography, or severe arrhythmia uncontrolled by medication.
• Pregnancy or lactation.
• Other conditions deemed unsuitable for enrollment by the investigator.