Leucine Combined With Radiotherapy and Chemotherapy as Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Single-Arm Clinical Study
Colorectal cancer (CRC), a prevalent gastrointestinal malignancy, is experiencing a rising incidence in China. Rectal cancer constitutes nearly half of all new CRC cases, with over half of these patients diagnosed at a locally advanced stage. While neoadjuvant chemoradiotherapy is the standard of care for these patients, it yields a pathological complete response in only 10-30% of cases, and the risk of recurrence and metastasis remains suboptimal. The role of amino acid metabolism in cancer therapy is gaining significant interest. Our preliminary data reveal that leucine-derived metabolite significantly impairs cellular DNA damage repair and enhances the efficacy of radiotherapy. However, it remains unknown whether combining leucine with chemoradiotherapy can improve tumor regression and survival in patients with locally advanced rectal cancer. The goal of this single-arm clinical trial is to evaluate the safety and efficacy of Leucine combined with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, potentially offering a new therapeutic option.
• The patient voluntarily participates in this study, signs the Informed Consent Form, demonstrates good compliance, and cooperate with follow-up;
• Aged 18 to 80 years (inclusive), both male and female are eligible;
• Histologically confirmed and assessed as locally advanced rectal adenocarcinoma (confirmed by MRI): cT3 or higher; or cN+;
• MRI confirms that the lower edge of the tumor is ≤10 cm from the anal verge;
• No prior anti-tumor treatment for rectal cancer (except for traditional Chinese medicine treatments);
• ECOG score of 0-1;
• Major organs or functions meet the following criteria (within 2 weeks before the test, no use of any blood components or growth factors for correction is allowed):
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelets ≥100×10\^9/L; Hemoglobin ≥10 g/dL; Serum albumin ≥3.0 g/dL; Total bilirubin ≤ ULN, ALT, AST, and/or AKP ≤2.5 × ULN; Serum creatinine ≤ ULN or creatinine clearance rate ≥60 mL/min; International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ ULN;
• Female patients of childbearing potential must agree to abstain from heterosexual intercourse or use reliable and effective contraception from the time of signing the informed consent form until at least 6 months after the last dose of study drug. A serum HCG test must be negative within 7 days before starting treatment, and the woman must not be breastfeeding. A woman is considered of childbearing potential if she has had menstruation, has not reached postmenopausal status (absence of menstruation for ≥12 consecutive months without any other cause), and has not undergone sterilization surgery (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy);
• Male patients with female partners of childbearing potential must agree to abstain from intercourse or use reliable and effective contraception from the time of signing the informed consent form until at least 6 months after the last dose of study drug. Male patients must also agree not to donate sperm during this period. Male patients with pregnant partners should use a condom, without the need for additional contraceptive methods.