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

NCT07755124 | Not Yet Recruiting Phase 1

• 1 other identifier: Approval No. 1281 (2026)
• Study Type: interventional
• Target: 140
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates whether an arginine-free diet combined with chemoradiotherapy can improve treatment outcomes in patients with locally advanced rectal cancer. Our previous study showed that an arginine-free diet is safe and may boost the body's immune response against tumors. The study has two phases. The first phase (6 patients) tests the safety of the diet. The second phase (134 patients) randomly assigns participants to receive either the arginine-free diet plus standard chemoradiotherapy or standard chemoradiotherapy alone. The arginine-free diet is provided as a liquid nutritional formula for 4 weeks. The main goal is to see if the diet increases the complete response rate (tumor disappearance). We will also evaluate survival outcomes, side effects, and quality of life.

Conditions

Rectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate (pCR + cCR)

  Complete response rate is defined as the proportion of participants achieving either pathological complete response (pCR) or clinical complete response (cCR). pCR is defined as no residual tumor cells in the resected tumor tissue and regional lymph nodes. cCR is defined as no evidence of residual tumor in the primary lesion and regional lymph nodes (ycT0N0) after neoadjuvant treatment, assessed by rectal examination, endoscopy, pelvic MRI (T2WI/DWI), and serum CEA level.

  From enrollment to postoperative pathological assessment, approximately 6 months

Study Arms (2)

Arginine-Deprived Diet + Chemoimmunotherapy + SCRT

EXPERIMENTAL

Dietary Supplement: Arginine-Deprived Diet; Radiation: Short-Course Radiotherapy (SCRT); Drug: CAPOX + PD-1 Inhibitor

Standard Chemoimmunotherapy with SCRT

ACTIVE COMPARATOR

Participants in the control arm receive standard chemoradiotherapy with normal diet. The treatment regimen includes CAPOX chemotherapy (oxaliplatin 130 mg/m² IV on day 1 + capecitabine 1000 mg/m² oral twice daily on days 1-14) combined with PD-1 inhibitor (200 mg IV on day 1) every 3 weeks for 6 cycles, plus short-course radiotherapy (25 Gy in 5 fractions) in the first week of cycle 2. Diet is unrestricted. No arginine-deprived diet is administered.

Radiation: Short-Course Radiotherapy (SCRT); Drug: CAPOX + PD-1 Inhibitor

Interventions

Arginine-Deprived Diet DIETARY_SUPPLEMENT

A nutritionally complete liquid formula providing 1978 kJ energy, 16.6 g protein, 22.2 g fat, 49.4 g carbohydrate, and 4.32 g dietary fiber per 100 g, with all essential amino acids except arginine. Participants receive the formula as a total diet replacement for 4 weeks during chemoradiotherapy. Daily intake is calculated based on standard body weight at 30 kcal/kg/day energy and 1.5 g/kg/day protein, typically 3.5-8.5 bottles per day (70 g/bottle, reconstituted in 300 mL warm water).

Arginine-Deprived Diet + Chemoimmunotherapy + SCRT

Short-Course Radiotherapy (SCRT) RADIATION

Short-course radiotherapy delivered at 25 Gy in 5 fractions over 5 consecutive days during the first week of Cycle 2 (C2D1-C2D5, day 21-28 of the treatment schedule).

Arginine-Deprived Diet + Chemoimmunotherapy + SCRT; Standard Chemoimmunotherapy with SCRT

CAPOX + PD-1 Inhibitor DRUG

CAPOX regimen (oxaliplatin 130 mg/m² IV on day 1 + capecitabine 1000 mg/m² oral twice daily on days 1-14) combined with PD-1 inhibitor (200 mg IV on day 1) every 3 weeks for 6 cycles.

Arginine-Deprived Diet + Chemoimmunotherapy + SCRT; Standard Chemoimmunotherapy with SCRT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• ANC ≥ 1.5 × 10⁹/L (no G-CSF within 14 days);
• Platelet count ≥ 100 × 10⁹/L;
• Hemoglobin ≥ 9 g/dL (no transfusion or erythropoietin within 7 days);
• Serum albumin ≥ 3.0 g/dL;
• Total bilirubin ≤ 1.5 × ULN;
• AST/ALT ≤ 2.5 × ULN;
• Creatinine clearance ≥ 50 mL/min or serum creatinine ≤ 1.5 × ULN;

You may not qualify if:

• 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.

Sponsors & Collaborators

• West China Hospital: lead

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Xuelei Ma

CONTACT

+86 13408410416; drmaxuelei@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Biotherapy Department, Deputy Director

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): August 14, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share