node-sparing radiotherapy combined with total neoadjuvant capox and sintilimab for mss middle and low rectal cancer

Conditions: Locally Advanced Rectal Cancer

Summary: phase ii clinical trial to evaluate node-sparing short-course radiation combined with total neoadjuvant capox and sintilimab for mss locally advanced rectal cancers.

this is an open-label, prospective, single-center phase ii clinical trial to evaluate node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with total neoadjuvant capox and pd-1 inhibitor (sintilimab) for patients with mss locally advanced of middle and low rectal cancer. a total of 47 patients will be enrolled in this trial. the primary endpoint is the complete response(cr) rate, which includes ccr and pcr. the organ preservation rate, tumor regression grade, 3-year dfs, 3-year os, and adverse effects will also be analyzed.

Eligibility criteria:
inclusion criteria: * patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy. * male or female aged 18-75. * patients diagnosed with low rectal cancer within 10 cm from the lower edge of the tumor to the anal verge by pelvic mri and anorectoscopy, the clinical stage is ct2n+m0/ct3-4an0/+m0, the lymph nodes are limited to the mesorectum, the circumferential resection margin is negative. * histologically confirmed rectal adenocarcinoma; genetic testing suggests msi-l or mss, or tumor biopsy immunohistochemistry reveals pmmr, that is, msh1, msh2, msh6, and pms2 are all positive. * eastern cooperative oncology group (ecog) 0-1. * no previous treatment(including anti-tumor therapy、immunotherapy or pelvic radiation). * adequate hematologic, hepatic, renal, thyroid and cardiac function: white blood cells ≥3500/mm3, neutrophils ≥1800/mm3, platelets ≥100,000/mm3, hemoglobin ≥100 g/l; activated partial thromboplastin time, prothrombin time and international normalized ratio ≤1.5 × uln; aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (uln), bilirubin ≤1.25 × uln, serum albumin ≥28 g/l. creatinine clearance ≥50 ml/mi, creatinine ≤1.5 × uln; * informed consent form signed. exclusion criteria: * patients with a previous history of malignant tumors besides rectal cancer. * patients with distant metastases before enrollment. * patients with positive internal or external iliac lymph nodes are assessed by mri or ct. * patients with obstruction, perforation, or bleeding that require emergency surgery. * patients with severe concomitant diseases and estimated survival time ≤ 5 years. * allergic to any component of the therapy. * patients with poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous adenocarcinoma. * patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy. * patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening. * factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities. * patients with congenital or acquired immune deficiency (such as hiv infection). * vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc. other conditions that investigators consider not suitable for this study.

Keywords: rectal cancer microsatellite stability node-sparing capox radiotherapy sintilimab immunotherapy neoadjuvant