| Eligibility |
Inclusion Criteria:
1. Aged over 18 years, men or women who are not pregnant;
2. ECOG PS 0/1 evaluated 14 days before enrollment, and expected survival >12 months
after liver resection;
3. Liver function: Child-Pugh score Class A or =7 Class B;
4. Patients with histologically- or clinically-confirmed CRLM(TxNxM1)and CRS>2;
5. Patients had completely resected Primary lesions and liver metastases as well as no
evidence of extrahepatic disease;
6. No complications such as bleeding, jaundice, infection, abdominal pleural effusion,
obstruction and perforation were observed within 7 days (including 7 days) before the
screening. The subjects recovered well after surgery, the surgical incision healed
well, the stitches were removed, and the drainage tube was removed;
7. Preoperative chemoradiotherapy was limited to neoadjuvant or conversion therapy;
8. Patients must have the ability to understand and voluntarily sign the informed
consent, and must sign an informed consent before starting any specific procedure for
the study;
9. Patients were considered capable of complying with the study protocol;
10. No medical comorbidities that could interfere with chemotherapy and immunotherapy or
targeted therapy, see exclusion criteria;
11. Pre-treatment tumour tissue sample (if available). If tumour tissue is available,
submit one formalin-fixed, paraffin-embedded (FFPE) tumour sample from a paraffin
block (preferred), or approximately 10-15 slides containing unstained, freshly cut,
serial sections, along with a relevant pathology report within 4 weeks of enrollment.
If the FFPE samples described above are not available, any type of sample (including
fine needle aspiration biopsy samples, cell mass samples [e.g., samples from pleural
effusion] and lavage samples) may also be accepted. An associated pathology report
should be provided with the sample. If tumour tissue is not available (e.g., exhausted
due to past diagnostic tests), subjects are still eligible for study participation;
12. Adequate haematological and organ function, based on the following laboratory results
obtained during the 14 days prior to enrollment (unless otherwise stated) : Absolute
neutrophil count (ANC)=1.5×10 9 /L (1500/µL), without supported granulocyte
colony-stimulating factor Lymphocyte count =0.5×10 9 /L (500/µL) Platelets = 75 × 10 9
/L(75, 000/µL) Haemoglobin= 85 g/L, blood transfusions may be permitted to meet this
criterion Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
alkaline phosphatase (ALP) = 5 × upper limit of normal (ULN); Serum bilirubin= 3 × ULN
Serum creatinine = 1.5 × ULN or calculated creatinine clearance =50 mL/min (using
Cockcroft-Gault formula) Serum albumin=28 g/L(2.8 g/dL) INR or aPTT=2 × ULN, or PT
prolonged = 3 s if patients did not receive anticoagulant therapy.
Albuminuria < 2+ tested by urinary cellulose (carried out within 14 days prior to
initiation of treatment); Patients with baseline albuminuria =2+ should have their
urine collected for 24 hours and must then confirm that albuminuria content within 24
hours is < 1g.
13. Any acute, clinically significant treatment-related toxicity (due to prior treatment)
must have resolved to = grade 1 prior to enrollment, except for hair loss;
14. HIV antibody test results were negative at screening;
15. Patients with active hepatitis B virus (HBV) infection: HBVDNA < 2000IU/mL acquired
within 28 days prior to enrollment, receiving anti-HBV therapy (in accordance with
local standard care, such as Entecavir) for at least 7 days prior to enrollment and
willing to continue treatment during the study period; Patients with active hepatitis
C virus (HCV) infection: HCVRNA < 2000IU/mL acquired within 28 days prior to
enrollment, receiving anti-HCV therapy for at least 7 days prior to enrollment and
willing to continue treatment during the study;
16. Women of childbearing age must undergo a negative pregnancy test (ßHCG) before
treatment, and women of childbearing age and men (who have sex with women of
childbearing age) must agree to use effective contraception uninterrupted during
treatment and for six months after the last therapeutic dose was administered.
Exclusion Criteria:
1. Colorectal cancer with extrahepatic metastasis;
2. Malignant abdominal effusion;
3. There were postoperative complications such as abdominal effusion, pleural effusion,
intestinal cavity perforation, bleeding and intestinal obstruction that needed
treatment.
4. History of soft meningitis
5. Current or past autoimmune diseases or immunodeficiency, including, but not limited
to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,
rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome,
Wegener's granuloma, Sjogren's syndrome, Guillain-Barre syndrome, or multiple
sclerosis, with the following exceptions: Subjects who had a history of
autoimmune-related hypothyroidism and were receiving thyroid hormone replacement
therapy were eligible; Subjects with controlled type 1 diabetes receiving insulin
therapy were eligible; Subjects with clinical manifestations of eczema, psoriasis,
chronic lichenia simple, or vitiligo only (e.g., excluding subjects with psoriatic
arthritis) are eligible if they meet all of the following criteria: 1. Skin rash area
must be < 10% body surface area 2. Good disease control at baseline with only
inefficient topical glucocorticoid therapy. 3. No acute exacerbations requiring
psoralen plus A-band ultraviolet radiation, methotrexate, retinoic acid, biologics,
oral calcineurin inhibitors, or high-performance or oral glucocorticoid therapy have
occurred in the previous 12 months;
6. Idiopathic pulmonary fibrosis, institutionalized pneumonia (e.g., bronchiolitis
obliterans), drug-induced or idiopathic pneumonia, or evidence of active pneumonia on
a chest computed tomography (CT) scan during screening. Radiation pneumonia was
present in the allowable area (fibrosis)
7. Active TB disease
8. Major cardiovascular disease (such as New York Heart Society Class II or worse heart
disease, myocardial infarction, or cerebrovascular accident), unstable arrhythmia, or
unstable angina in the 3 months prior to enrollment;
9. A history of congenital long QT syndrome or a corrected QT interval >500ms at
screening (calculated using Fridericia's method);
10. A history of uncorrected electrolyte disturbances such as serum potassium, calcium, or
magnesium
11. Received major surgery within 4 weeks prior to the enrollment (except for diagnosis)
or expected to require major surgery during the study period;
12. Malignancies other than CRC that have developed within 5 years prior to screening,
with the exception of those with a negligible risk of metastasis or death (e.g.,
5-year OS rate > 90%), such as adequately treated cervical carcinoma in situ,
non-melanoma skin cancer, localized prostate cancer, duct carcinoma in situ, or stage
I uterine cancer;
13. Severe infections, including but not limited to hospitalization due to infection,
bacteremia, or severe pneumonia complications, occurred in the 4 weeks prior to the
enrollment;
14. Therapeutic antibiotics were given orally or intravenously within 2 weeks prior to the
enrollment. Subjects who received prophylactic antibiotics (for example, to prevent
urinary tract infections or exacerbations of COPD) were eligible;
15. Previous allogeneic stem cell or solid organ transplantation;
16. Received live attenuated vaccine within 4 weeks prior to the enrollment, or expected
to receive such vaccine during sintilimab treatment or within 5 months after the last
dose;
17. With untreated or incompletely treated esophageal and/or gastric varicose veins
associated with bleeding or at high risk of bleeding. Prior to enrollment, subjects
must undergo ultrasound, CT, MRI, or liver elasticity tests, assess the size of all
varicose veins (small to large), and be treated according to local standard care.
Subjects who received the corresponding examination within 6 months prior to the
enrollment do not need to be re-examined;
18. Co-infection with HBV and HCV. Subjects with a history of HCV infection but negative
PCR results for HCV RNA are considered not infected with HCV;
19. Symptomatic, untreated, or progressive central nervous system (CNS) metastases.
Asymptomatic subjects whose CNS lesions have been treated are eligible as long as they
meet all of the following criteria: They must have measurable lesions outside the CNS
according to RECIST v1.1; Subjects had no history of intracranial or spinal bleeding;
Metastases are limited to the cerebellar or supratentorial regions (i.e., no midbrain,
pontine, medullary, or spinal cord metastases); No evidence of progress between
completion of CNS oriented therapy and initiation of study therapy; Subjects had not
received stereotactic, whole brain radiation, and/or neurosurgical resection within 28
days prior to the enrollment; There was no need for continuous use of glucocorticoids
to treat CNS disease. A steady dose of anticonvulsant therapy is permitted.
Asymptomatic subjects with newly detected CNS metastases at the time of screening are
eligible after radiotherapy or surgery, and no need for repeated screening of brain
scan results;
20. Refuse follow-up and participating in other clinical trials that may interfere with
this study;
21. Patients are not suitable for enrollment judged by investigators.
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