Phase Ib/II Trial of Serine/Glycine-Restricted Diet With Chemoradiotherapy for Rectal Cancer (SG-RCT)

Inclusion Criteria:

• Written informed consent obtained prior to any study-related procedures.
• Male or female, aged 18-80 years.
• Histologically confirmed locally advanced mid-to-upper rectal cancer, staged as cT3, cT4, or node-positive by pelvic MRI.
• ECOG performance status score of 0 or 1.
• NRS-2002 score < 3.
• BMI ≥ 18.5 kg/m².
• Capable of oral intake or via feeding tube, and able to tolerate enteral nutrition.
• Adequate organ function meeting the following laboratory criteria:

ANC ≥ 1.5×10⁹/L (without G-CSF within 14 days);

Platelet count ≥ 100×10⁹/L;

Hemoglobin ≥ 9 g/dL (without transfusion or erythropoietin within 7 days);

Serum albumin ≥ 3.0 g/dL;

Total bilirubin ≤ 1.5× ULN;

AST and ALT ≤ 2.5× ULN;

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

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

Urine protein < 2+;

Cardiac enzymes within normal range.

• Female patients of childbearing potential must have a negative serum pregnancy test within 3 days prior to study treatment and agree to use highly effective contraception for at least 6 months after the last dose.
• All patients at risk of pregnancy must use highly effective contraceptive methods during the treatment period and up to 120 days (or 180 days after last chemotherapy dose) after the last dose of study treatment.

Exclusion Criteria:

• Stage I or Stage IV rectal cancer.
• Cognitive impairment or psychiatric disorders preventing comprehension of the study content.
• Central nervous system or meningeal metastases.
• Clinically symptomatic moderate to severe ascites requiring therapeutic paracentesis.
• 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, intra-abdominal abscess; gastrointestinal bleeding (CTCAE grade ≥ 3 within 6 months or grade ≥ 2 within 3 months before study treatment).
• Any other condition that may affect the study results or lead to forced discontinuation as judged by the investigator (e.g., alcohol or drug abuse, serious concurrent diseases, severe laboratory abnormalities).
• Known allergy to the study drugs or nutritional powder active ingredients or excipients.
• Poorly controlled diabetes mellitus.
• Severe cardiovascular/cerebrovascular diseases, including CVA, TIA, myocardial infarction, major vascular disease within 6 months; uncontrolled symptomatic cardiac disease (e.g., unstable angina, NYHA class II or higher heart failure, LVEF < 50% on echocardiography, or severe uncontrolled arrhythmia).
• Pregnant or lactating women.
• Any other condition that the investigator considers unsuitable for enrollment.