| Eligibility |
Inclusion Criteria:
1. Aged 18-70 years old, both genders.
2. ECOG PS 0-1 points.
3. Hepatocellular liver cancer with a clinical diagnosis consistent with primary
hepatocellular liver cancer and a lesion consistent with the Primary Liver Cancer
Diagnostic and Treatment Standards (2019) Edition.
4. The hepatobiliary MDT of Cancer Hospital of Chinese Academy of Medical Sciences (MDT)
discussed the case as potentially resectable requiring neoadjuvant chemotherapy.
5. Locally advanced, potentially resectable tumors. Ruptured liver tumor or adjacent
organ invasion without extrahepatic metastasis (imaging confirmed).
Hepatocellular carcinoma combined with cancerous thrombus in a branch of a grade 1 or 2
vasculature (portal vein, hepatic vein, bile duct) (imaging confirmed).
Lymph node metastasis (image confirmed). Liver tumor = 5 cm; multiple tumors with = 3
tumors, but located in one lobe (imaging [CT, MRI or ultrasound]) Hepatocellular carcinoma
tumors located in the middle lobe (segment IV, V, VIII) or caudal lobe of the liver;
hepatocellular carcinoma tumors within 1 cm of a branch of a grade 1 or 2 vasculature
(portal vein, hepatic vein, bile duct) or involving the above-mentioned vasculature
(expected cut edge < 1 cm).
Tumor with satellite foci or subfoci. Tumor without envelope or incomplete tumor with
envelope, multi-nodal fusion. 6. NRS =3 points. 7. Patients who have not received any
previous antineoplastic drug treatment. 8. At least 1 measurable lesion that meets RECIST
1.1 criteria. 9. Liver function Child-Pugh score: grade A-B (=7). 10. Expected survival > 3
months. 11. Relevant indicators meet the following criteria:
1. blood routine examination HB=90 g/L; ANC=1.5×109/L; PLT=75×109/L;
2. CMP ALB =30g/L; ALT and AST< 2.5ULN; TBIL =1.5 ULN; Cr =1.5ULN 12. Women of
childbearing age (18-49 years covered by this protocol) must have a negative pregnancy
test (serum or urine) result within 14 days prior to enrollment and voluntarily use an
appropriate method of contraception during the observation period and for 8 weeks
after the last dose of study drug; for men, they should be surgically sterilized or
agree to use an appropriate method of contraception during the observation period and
for 8 weeks after the last dose of study drug.
13. Patients with HBV or HCV infection are required to be on antiviral therapy for the
duration of the trial.
Subjects voluntarily enrolled in this study, signed informed consent, good compliance and
cooperation with follow-up.
Exclusion Criteria:
- Patients will not be entered into this study if they meet any of the following criteria.
1. History of other malignancies within the previous 5 years or concurrently, except for
cured basal cell carcinoma of the skin and carcinoma in situ of the cervix and
papillary thyroid cancer
2. History of ruptured esophagogastric fundic varices, hepatic encephalopathy, massive
ascites, and abdominal infection
3. Patients with previous use of other anti-angiogenic drugs, immunotherapeutic drugs,
radiotherapy or systemic chemotherapy
4. Prior use of immunosuppressive drugs, excluding nasal spray and inhaled
corticosteroids or physiologic doses of systemic steroids (i.e., no more than 10 mg
days of prednisolone or equivalent pharmacologic doses of other corticosteroids),
within 14 days prior to the first administration of kareolizumab
5. Known hypersensitivity to apatinib, carrilizumab, oxaliplatin, or drug excipients; or
severe allergic reactions to other monoclonal antibodies
6. Live attenuated vaccines administered within 4 weeks prior to the first dose or
scheduled to be administered during the study.
7. Known uncontrolled or symptomatic active central nervous system (CNS) metastases as
evidenced by the presence of clinical signs, cerebral edema, spinal cord compression,
carcinomatous meningitis, soft meningeal disease, and or progressive growth. Patients
with a history of CNS metastases or spinal cord compression who are clearly treated
and clinically stable after discontinuation of anticonvulsants and steroids for 4
weeks prior to the first dose of the study may be enrolled in the study.
8. The presence of > grade 1 peripheral neuropathy
9. The presence of any active autoimmune disease or a history of autoimmune disease
10. Presence of the following within 6 months prior to study entry: myocardial infarction,
severe unstable angina, NYHA class 2 or higher cardiac insufficiency, poorly
controlled arrhythmias (including QTcF intervals >450 ms in men and >470 ms in women,
QTcF intervals calculated using the Fridericia formula), symptomatic congestive heart
failure, cerebrovascular accident ( including transient ischemic attack or symptomatic
pulmonary embolism).
11. Hypertension that is not well controlled with antihypertensive medication (systolic
blood pressure = 140 mmHg or diastolic blood pressure = 90 mmHg).
12. Abnormal coagulation (INR > 1.5 or APTT > 1.5 x ULN) with bleeding tendency or on
thrombolytic or anticoagulant therapy
13. Known hereditary or acquired bleeding and thrombotic tendencies, e.g., hemophilia,
coagulation disorders, thrombocytopenia, hypersplenism, etc.
14. Presence of significant coughing up of fresh blood, or hemoptysis of half a teaspoon
(2.5 ml) or more per day within 2 months prior to study entry
15. The presence of clinically significant bleeding symptoms or a definite bleeding
tendency within 3 months prior to study entry, such as gastrointestinal bleeding,
hemorrhagic gastric ulcer, fecal occult blood +++ or more at baseline, or vasculitis
16. Arteriovenous thrombotic events such as cerebrovascular accidents (including transient
ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and
pulmonary embolism that occurred within 6 months prior to study entry
17. Known presence of hereditary or acquired bleeding and thrombotic tendencies (e.g.
hemophiliacs, coagulation disorders, thrombocytopenia, hypersplenism, etc.)
18. The need for long-term anticoagulation therapy with warfarin or heparin, or the need
for long-term antiplatelet therapy (aspirin = 300 mg days or clopidogrel = 75 mg days)
19. Concurrent severe infection (e.g., requiring intravenous antibiotics, antifungal or
antiviral drugs) within 4 weeks prior to the first dose, or fever of unknown origin
>38.5°C prior to the first dose during the screening period
20. Participation in any other drug clinical study within 4 weeks prior to the first dose,
or no more than 5 half-lives from the last study dose
21. A known history of psychotropic substance abuse or drug use
22. The presence of other serious physical or mental illnesses or abnormal laboratory
tests that may increase the risk of participation in the study or interfere with the
results of the study, and patients who, in the opinion of the investigator, are not
suitable for participation in this study.
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