Leucine Plus Radiochemotherapy for Neoadjuvant Treatment of Locally Advanced Rectal Cancer

NCT07359989 | Recruiting

• 1 other identifier: IIT 2025-0428
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rectal Cancer

Keywords

Rectal Cancer; Leucine

Outcome Measures

Primary Outcomes (2)

• The Pathological complete response (pCR) rate

  The definition of pCR is that after surgery, in the pathological evaluation of the resected rectal cancer lesion, mesorectum, and regional lymph node samples, there are no visible tumor cells under the microscope. Tumor cells refer to viable tumor cells, excluding degenerated or necrotic cells. Pools of acellular mucin should not be assessed as residual tumor.

  From enrollment to the end of treatment at 16 weeks.

• Clinical complete response (cCR) rate

  The cCR assessment is defined by the fulfillment of the following three criteria: 1. Digital rectal examination of the original tumor area shows normal findings, with no palpable tumor masses. 2. Endoscopy reveals white, flat mucosal scars accompanied by surrounding capillary ectasia, without evidence of tumor ulcers or nodules; mucosal biopsy results are negative for cancer cells. 3. Contrast-enhanced MRI of the rectum shows: On T2-weighted images, only low signal intensity (dark on T2) is present without intermediate T2 signal intensity, and there are no signs of enlarged lymph nodes. there is no visible signal on diffusion-weighted (DW) images.

  From enrollment to the end of treatment at 12 weeks.

Secondary Outcomes (5)

• Adverse events.

  From enrollment to the end of treatment at 3 years.

• The rate of TRG0

  From enrollment to the end of treatment at 16 weeks

• The rate of R0 resection

  From enrollment to the end of treatment at 16 weeks.

• Event-Free Survival

  From enrollment to the end of treatment at 3 years

• Overall Survival

  From enrollment to the end of treatment at 3 years

Study Arms (1)

Leucine plus Radiotherapy and Chemotherapy

EXPERIMENTAL

Leucine plus radiotherapy and chemotherapy as neoadjuvant therapy

Dietary Supplement: Oral administration of Leucine

Interventions

Oral administration of Leucine DIETARY_SUPPLEMENT

Oral administration of leucine during radiotherapy

Leucine plus Radiotherapy and Chemotherapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Patients with locally recurrent rectal cancer after previous treatment;
• Patients assessed by the investigator as having initially unresectable rectal cancer or those deemed unable to tolerate surgery;
• Clinical or imaging evidence suggests distant metastasis or positive lateral lymph nodes;
• Patients with multiple colorectal cancer lesions;
• Clinical or imaging evidence suggests bowel obstruction or perforation, or the investigator evaluates a high risk of perforation or bleeding;
• Factors deemed by the investigator to make the patient unsuitable for long-course radiotherapy;
• Severe cardiovascular or cerebrovascular diseases, including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction, or significant vascular disease (such as an aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to enrollment; poorly controlled cardiac symptoms or diseases, such as unstable angina, NYHA class II or higher heart failure, left ventricular ejection fraction \<50% by echocardiography, or severe arrhythmias not controlled by medication;
• History of active pulmonary tuberculosis detected by medical history or CT, active pulmonary tuberculosis within 1 year before enrollment, or a history of active tuberculosis more than 1 year ago that was not properly treated;
• Major surgery within 3 months before starting study treatment (major surgery is defined as surgery performed under general anesthesia); presence of non-healing wounds (severe, non-healing or dehiscent), active peptic ulcers, or untreated fractures;
• Difficulty swallowing or other factors affecting oral medication use;
• Contraindications to MRI;
• Active autoimmune disease or history of autoimmune diseases (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, colitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism \[patients controlled by thyroid hormone replacement therapy can be included\]); patients with skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis, alopecia), controlled type 1 diabetes treated with insulin, and childhood asthma that has fully resolved and requires no intervention in adulthood may be included (patients requiring bronchial dilation for asthma cannot be included);
• History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation;
• Severe infections within 4 weeks before the first use of the study drug (CTCAE \> Grade 2), such as severe pneumonia, bacteremia, or infections requiring hospitalization; active lung inflammation on baseline chest imaging, signs and symptoms of infection requiring oral or intravenous antibiotics within 2 weeks before the first use of the study drug, except for prophylactic antibiotics;
• Current or past history of interstitial lung disease or interstitial pneumonitis requiring steroid therapy, or other conditions (e.g., lung fibrosis, organizing pneumonia such as bronchiolitis obliterans) that may interfere with the assessment and management of immune-related lung toxicity, evidence of active pneumonia on screening chest CT, or severely impaired lung function;

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital Of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

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

Central Study Contacts

Haiyan Chen, Doctor

CONTACT

86-86992821; chenhaiyan@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 22, 2026
• Study Start: June 11, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 22, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)