A Randomized Controlled Trial of Dietary Arginine Deprivation Combined With Chemoradiotherapy for Neoadjuvant Treatment of Locally Advanced Rectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 140
- 主要终点
- Complete Response (CR) Rate (pCR + cCR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •NRS-2002 score <
- •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;
- •INR ≤ 1.5 × ULN, PT and APTT ≤ 1.5 × ULN;
- •Urine protein < 2+ (if ≥ 2+, 24-hour urine protein < 2.0 g allowed);
- •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).
排除标准
- •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.
研究组 & 干预措施
Arginine-Deprived Diet + Chemoimmunotherapy + SCRT
干预措施: CAPOX + PD-1 Inhibitor (Drug)
Arginine-Deprived Diet + Chemoimmunotherapy + SCRT
干预措施: Arginine-Deprived Diet (Dietary Supplement)
Standard Chemoimmunotherapy with SCRT
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.
干预措施: Short-Course Radiotherapy (SCRT) (Radiation)
Standard Chemoimmunotherapy with SCRT
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.
干预措施: CAPOX + PD-1 Inhibitor (Drug)
Arginine-Deprived Diet + Chemoimmunotherapy + SCRT
干预措施: Short-Course Radiotherapy (SCRT) (Radiation)
结局指标
主要结局
Complete Response (CR) Rate (pCR + cCR)
时间窗: From enrollment to postoperative pathological assessment, approximately 6 months
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.
次要结局
未报告次要终点
研究者
Xuelei Ma MD
Biotherapy Department, Deputy Director
West China Hospital