| Eligibility |
Inclusion Criteria:
- Histologically confirmed colorectal adenocarcinoma with T4bNxM0 and radical operation
cannot be achieved by investigator's evaluation
- Immunohistochemistry and/or genetic testing confirmed pMMR/MSS
- Initial diagnosed or recurrent patients will be accepted, patients with recurrence
should not have received any treatment include chemotherapy, targeted therapy or
immunotherapy within 1 month or radiotherapy within 1 year
- Measurable disease according to the Response Evaluation Criteria In Solid Tumors
(RECIST) 1.1 criteria and haven't received any local treatment.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
- Absence of distant metastasis confirmed by CT, MRI or PET/CT
- Adequate hematologic and organ function, defined by protocol-specified laboratory test
results, obtained within 7 days before first dose. Absolute neutrophil count
=1500/mm3, platelet =100,000/mm3, Hb =10g/dl, serum creatinine =1.5 times ULN,
creatinine clearance rate =50mL/min, ALT and AST =2.5 times ULN, INR or aPTT =1.5
times ULN (INR =2 times ULN and aPTT in normal range for patients who are on
prophylactic anticoagulant therapy within 14 days before study treatment), total
bilirubin level =2 times ULN (within 7 days before study treatment).
- Women of childbearing age should confirm that serum pregnancy test is negative and
agree to use effective contraceptive methods during study treatment and the following
60 days.
- Life expectancy> 3 months
- Signed and written informed consent
Exclusion Criteria:
- Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
- Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
- Contraindications of bevacizumab
- Hypersensitivity to other monoclonal antibodies.
- Any active, known or suspected autoimmune disease.
- Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or
greater extent.
- History of one of the following diseases: idiopathic pulmonary fibrosis, organized
pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia
and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT
screening.
- Major surgery within 4 weeks before enrollment and haven't fully recovered from the
previous surgery.
- Active bleeding or abnormal coagulation (aPTT >43s or INR >1.5 times ULN), or having a
tendency to bleed or receiving thrombolytic or anticoagulant therapy.
- Previously received allogeneic stem cell or parenchymal organ transplantation.
- Any significant clinical or laboratory abnormality that the investigator considers to
influence the safety assessment, eg. uncontrolled active infection, uncontrolled
diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade
II or above peripheral neuropathy, congestive heart failure, heart disease (class II
or higher) as defined by the New York College of Cardiology, myocardial infarction
within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis,
chronic kidney disease, abnormal thyroid function and previous or co-existing
malignancies.
- History of uncorrected serum electrolyte disturbances such as potassium, calcium and
magnesium.
- HIV infection.
- Active hepatitis B or hepatitis C.
- Pregnancy or lactation period, or unwilling to use contraception during the trial.
- With other malignancy within 5 year, except cervical carcinoma in situ, basal or
squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.
- Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other
immunosuppressive agents within 14 days before enrollment.
- Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have
received anti-TB treatment within 1 year.
- Active infection, or treatment with oral or intravenous antibiotics within the first 2
weeks prior to neoadjuvant therapy, except prophylactic administration.
- Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection
within 4 weeks before neoadjuvant therapy.
- Previous participation in other clinical trials within 4 weeks before neoadjuvant
therapy.
- Any other disease, metabolic disorder, abnormal physical examination or abnormal
laboratory results that may constrain the use of trial drug, or affect the reliability
of study results, or lead to high risk of treatment complications, or affect patient
compliance.
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