Circulating Tumor DNA-guided Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer (CINTS-R)
Locally Advanced Rectal Carcinoma, Circulating Tumor DNA
About this trial
This is an interventional treatment trial for Locally Advanced Rectal Carcinoma focused on measuring Locally advanced rectal cancer, circulating tumor DNA, Neoadjuvant chemoradiotherapy, Total neoadjuvant therapy, Randomized Controlled Trial
Eligibility Criteria
Inclusion Criteria: Aged 18-75 years; ECOG score 0-2; Rectal adenocarcinoma confirmed by pathology; The lower margin of the tumor was less than 12cm from the anal margin; Patients with clinical stage cT3-4N0M0 or cTanyN+M0; Newly treated patients who have not received treatment including radiotherapy, chemotherapy and surgery; Liver, kidney and other organs have good function and can tolerate radiotherapy, chemotherapy and surgery; Patients and family members can understand the study protocol, voluntarily participate in the study and sign informed consent. Exclusion Criteria: ECOG score > 2; Patients with multiple primary colorectal cancers; A history of other malignant tumors (other than cured basal cell carcinoma, cervical carcinoma in situ, surgically treated localized prostate cancer, or surgically resected breast ductal carcinoma in situ) within the past 5 years; Complicated with intestinal obstruction, intestinal perforation, gastrointestinal bleeding and other patients requiring emergency surgery; pregnant or lactating women; Patients with a history of severe mental illness, immune disease, hormone medication; Patients contraindicated by MRI examination, chemoradiotherapy, immunotherapy or surgery; Participated in other clinical researchers in the past 3 months; Any other circumstances that the investigator considers inappropriate for inclusion.
Sites / Locations
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences,Recruiting
Arms of the Study
Arm 1
Arm 2
No Intervention
Experimental
Traditional neoadjuvant chemoradiotherapy group
ctDNA-guided neoadjuvant treatment group
Eligible patients randomized into arm A will receive traditional neoadjuvant chemoradiotherapy, including long-course radiotherapy with a total number of 45-50.4Gy in 25-28 fractions, and with concurrent 3 times of oral capecitabine, the strategies of capecitabine are: During radiotherapy: capecitabine 1650mg/m2/d, orally administered twice a day, d1-d14, every 3 weeks as a course; During the non-radiotherapy period: capecitabine 2000mg/m2/d, orally administered twice daily, d1-d14, every 3 weeks as a course
After sequencing tumor tissue, those with MSI-H/TMB-H or POLD/POLE2 mutation willed be arranged to receive immune therapy following NCRT,Terelizumab,200mg. The others are arranged to randomly receive TNT (VAF>0.4%) or NCRT (VAF<0.4%) according to VAF value by the level of ctDNA. TNT: Long course radiotherapy combined with 2 courses of single-agent capecitabine chemotherapy → 6 courses of CapeOX (Capecitabine 2000mg/m2/ day, twice orally, d1-14; Oxaliplatin 100-130mg/m2, intravenous infusion, d1; Every 3 weeks for a course of treatment.) chemotherapy was performed 2 to 3 weeks after the end of chemotherapy.