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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Oral administration of leucine during radiotherapy
Second Affiliated Hospital Of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGThe 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.
Time frame: 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.
Time frame: From enrollment to the end of treatment at 12 weeks.
Adverse events.
The incidence, type, and severity of adverse events (AEs), serious AEs, and immune-related AEs (irAEs) were assessed in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0).
Time frame: From enrollment to the end of treatment at 3 years.
The rate of TRG0
Complete regression, defined as no residual tumor cells in the primary tumor and regional LNs (ypT0N0)
Time frame: From enrollment to the end of treatment at 16 weeks
The rate of R0 resection
R0 resection is defined as the removal of the rectal cancer lesion during surgery with no tumor cells present within 1 mm of the resection margins.
Time frame: From enrollment to the end of treatment at 16 weeks.
Event-Free Survival
Event-Free Survival (EFS) was defined as the period from the date of first treatment administration to the date of the first documented relevant event, where relevant events include disease progression that leads to inoperability, local recurrence or distant metastasis after surgery, and death due to any cause.
Time frame: From enrollment to the end of treatment at 3 years
Overall Survival
OS (Overall Survival) is defined as the period from the date of first treatment administration to the date of death due to any cause.
Time frame: From enrollment to the end of treatment at 3 years
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