Standard Systemic Therapy Combined With High/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer

Inclusion criteria

• Age between18 and 75 years old.
• An Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum.
• At least one evaluable metastatic lesion for radiotherapy and evaluation according to RECIST 1.1.
• Treatment naive (first-line cohort) and progressed on after first-line therapy or stopped first-line therapy due to unacceptable toxic effects (second-line cohort).
• Prior radiotherapy completed at least 4 weeks before enrollment.
• Adequate bone-marrow, hepatic, and renal function: neutrophils ≥ 1.5 × 10\^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10\^9/L, ALT/ AST≤2.5 ULN, Cr≤1 ULN.
• Sign the informed consent and have good compliance.

Exclusion criteria

• Neutrophil \< 1.5×10\^9/L, PLT \< 100×10\^9/L (PLT \< 80×10\^9/L in patients with liver metastasis), or Hb \< 90g/L; blood transfusion within 2 weeks before enrollment is not allowed to meet the enrollment criteria.
• TBIL \> 1.5 ULN, or TBIL \> 2.5 ULN in patients with liver metastasis. AST or ALT \> 2.5 ULN, or ALT and / or AST \> 5 ULN in patients with liver metastasis.
• Cr \> 1.5 ULN, or creatinine clearance \< 50ml / min (calculated according to Cockcroft Gault formula).
• APTT \> 1.5 ULN, PT \> 1.5 ULN (subject to the normal value of the clinical trial research center).
• Serious electrolyte abnormalities. Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h. Uncontrolled hypertension: SBP \>140mmHg or DBP \> 90mmHg. The presence of gastrointestinal diseases such as gastric or duodenal active ulcers, ulcerative colitis or unresected tumours with active bleeding; or other conditions likely to cause gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation or gastrointestinal fistula after surgical treatment.
• A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months.
• A history of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF\<50%).
• Uncontrolled malignant pleural effusion, ascites, or pericardial effusion. History of anti-PD-1, PD-L1, PD-L2, CTLA-4 or any other specific T cell co-stimulation or checkpoint pathway targeted therapy.
• The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive tumour, or carcinoma in situ, or T1).
• A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10\^4/ml), HCV infection or HCV DNA positive(≥1×10\^3/ml) and liver cirrhosis.
• Pregnant or lactating women or women who may be pregnant have a positive pregnancy test before the first medication; Or the female participants themselves and their partners who were unwilling to implement strict contraception during the study period.
• The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.
• Serious mental abnormalities. The diameter of brain metastasis is greater than 3cm or the total volume is greater than 30cc.
• Clinical or radiological evidence of spinal cord compression, or tumours within 3 mm of the spinal cord on MRI.