| Eligibility |
Inclusion Criteria:
- 1. Written informed consent should be signed before implementing any trial-related
procedures 2. Patients with age =18 years ,=75 years old. 3. ECOG PS scores 0-1 4.
Histologically/cytologically confirmed unresectable or metastatic Intrahepatic
Cholangiocarcinoma and gallbladder cancer 5. Child Pugh stage A 6. Estimated survival
> 12 weeks 7. According to the diagnostic criteria of NCCN(National Comprehensive
Cancer Network ) guidelines for intrahepatic cholangiocarcinoma and gallbladder
cancer, the patients were diagnosed as intrahepatic cholangiocarcinoma and gallbladder
cancer not suitable for radical resection: unable to obtain R0 resection, multiple
liver, beyond hilar lymph node metastasis and distant metastasis 8. No systemic
therapy for unresectable or metastatic biliary tract cancer; Patients who had received
one regimen of adjuvant therapy and had a relapse more than 6 months after the end of
chemotherapy were eligible.
9. At least one measurable lesion according to RECIST V1.1 The diameter of the target
lesion was =1cm as accurately measured by enhanced magnetic resonance imaging (MRI) or
enhanced computed tomography (CT), and the study target lesion had not received
previous local treatment (including but not limited to HAIC, radiofrequency ablation,
argon-helium knife, radiotherapy, and other local treatment methods) 10. Sufficient
organ and bone marrow functions, with the laboratory test values within 14 days before
the enrollment meeting the following requirements (no blood components, cell growth
factors, albumin, and other drugs via intravenous or subcutaneous administrations are
allowed for correction treatment within the first 14 days after the laboratory test
results are obtained). The specific information is as follows:
1. Routine blood test: white blood cell = 4.0 × 109/L absolute neutrophil count
(ANC) = 1.5 × 109/L; platelet count (PLT) = 80 × 109/L; hemoglobin (HGB) = 9.0
g/dL.
2. Hepatic function: total bilirubin (TBIL) = 3 × upper limit of normal (ULN),
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5 × ULN.
3. Renal function: serum creatinine (Cr) = 1.5 × ULN or eGFR=60%,clearance of
creatinine (CCr) = 60 mL/min (Cockcroft Gault formula);
4. Blood coagulation function: international normalized ratio (INR) and activated
partial thromboplastin time (APTT) = 1.5 × ULN.
5. Normal cardiac function with left ventricular ejection fraction (LVEF)=50%
measured by two-dimensional echocardiography; 11. Patients were eligible for HAIC
surgery as prespecified by the study center, without any contraindications, and
could receive HAIC treatment.
12. Male or female patients of childbearing potential volunteered to use an effective
method of contraception, such as dual barrier methods, condoms, oral or injectable
contraceptives, intrauterine devices, etc. during the study and for 6 months after the
last study medication. "All female patients will be considered fertile unless they
have undergone natural menopause, artificial menopause, or sterilization (e.g.,
hysterectomy, bilateral adnophorectomy, or radioactive ovarian irradiation)."
Exclusion Criteria:
- 1. Participated in other clinical trials of antineoplastic drugs within 4 weeks before
enrollment.
2. History of liver resection, TACE treatment, and any previous immune or targeted
therapy; 3. Liver metastases of 70% or more of the total liver volume as determined by
the investigator.
4. History of prior or planned any organ transplantation. 5. Patients with obstructive
jaundice who did not reduce jaundice as expected. 6. Other malignant tumors in the
past 5 years, excluding basal cell or squamous cell carcinoma of the skin after
radical surgery, or carcinoma in situ of the cervix.
7. Patients with confirmed or suspected symptomatic active brain or meningeal
metastases.
8. Received any surgery (except biopsy) or invasive treatment or operation within 4
weeks before enrollment and the surgical incision was not completely healed (except
venous catheterization, puncture drainage, etc.).
9. Electrolyte abnormalities that were judged by the investigator to be clinically
significant..
10. Patients have current drug-uncontrolled hypertension defined as systolic blood
pressure =150 mmHg and/or diastolic blood pressure =100 mmHg.
11. Urine routine test showed urinary protein =2+, and 24 h urinary protein amount
>1.0g.
12. Patients whose tumors were judged by the investigator to be highly likely to
invade vital blood vessels and cause fatal bleeding during the follow-up study.
13. Patients with evidence or history of significant bleeding tendency within 3 months
before enrollment (bleeding within 3 months >30 mL, hematemesis, melena,
hematochezia), hemoptysis (within 4 weeks>5 mL of fresh blood); Patients with a
history of hereditary or acquired bleeding or coagulopathy. Patients had clinically
significant bleeding symptoms or clear bleeding tendency within 3 months before
enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.
14. Clinically significant cardiovascular disease, including but not limited to acute
myocardial infarction, severe/unstable angina, or coronary artery bypass grafting
within 6 months before enrollment; New York Heart Association (NYHA) classification of
congestive heart failure >Grade 2; Ventricular arrhythmias requiring medical therapy;
Electrocardiogram (ECG) showed QT c interval =480 msec.
15. Women who are pregnant (with a positive pregnancy test before medication) or
breastfeeding.
16. Any other medical condition, clinically significant metabolic abnormality,
physical examination abnormality, or laboratory abnormality in which there is reason
to suspect that the patient has a disease or condition (e.g., having seizures
requiring treatment) that would be inappropriate for use of the study drug, or that
would affect interpretation of the study results or place the patient at high risk, in
the investigator's judgment.
17. Severe active or uncontrolled infection (=CTCAE grade 2 infection), known human
immunodeficiency virus (HIV) infection; Known history of clinically significant liver
disease, including viral hepatitis [known hepatitis B virus (HBV) carriers must
exclude active HBV infection, i.e., HBV DNA positive (> 1×104 copies /mL or >2000 IU/
mL), known hepatitis C virus (HCV) infection with positive HCV RNA (>1×103 copies
/mL), or other hepatitis, cirrhosis.
18. Patients with any active, known or suspected autoimmune disease (including but not
limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vasculitis,
glomerulonephritis, uveitis, hypophysitis, hyperthyroidism, etc.) Patients with any
active, known or suspected autoimmune disease (including but not limited to myasthenia
gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
arthritis, enteritis, multiple sclerosis, vasculitis, glomerulonephritis, uveitis,
hypophysitis, hyperthyroidism, etc).
19. Known allergic reactions to other monoclonal antibodies or to any component of
surufatinib.
20. According to the investigator's judgment, patients have other factors that may
affect the results of the study or lead to the forced termination of the study, such
as alcohol abuse, drug abuse, other serious diseases (including mental diseases)
requiring combined treatment, family or social factors, etc., which will affect the
safety of patients.
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