| Eligibility |
Inclusion Criteria:
1. The subjects voluntarily joined the study and signed the informed consent, with good
compliance and follow-up;
2. Inoperable or metastatic intrahepatic bile duct carcinoma confirmed by histopathology
or cytology;
3. In accordance with the NCCN guidelines for intrahepatic cholangiocarcinoma diagnosis
criteria, intrahepatic cholangiocarcinoma not suitable for radical resection was
confirmed: R0 resection could not be obtained, liver was multiple, lymph node
metastasis beyond the hepatic portal area and distant metastasis;
4. Male or female between the ages of 18 and 75 (including boundary values);
5. ECOG score: 0-1; Expected survival =12 weeks;
6. Liver function Child-Pugh grade A;
7. Have not received systematic treatment for inoperable or metastatic biliary tract
cancer; Patients who had received adjuvant or neoadjuvant chemotherapy of one regimen
and relapsed 6 months after the end of chemotherapy could be enrolled;
8. At least one measurable lesion (according to RECIST 1.1); Magnetic resonance imaging
(MRI) enhancement or computed tomography (CT) enhancement were used to accurately
measure the diameter of the lesion =1cm, and the study target lesion had not
previously received local treatment (including but not limited to HIAC, radiofrequency
ablation, argon helium knife, radiation therapy and other local treatments);
9. No serious organic diseases of heart, lung, brain and other organs;
10. The main organs and bone marrow functions are basically normal:
1. Blood routine: white blood cells = 4.0 x 109/L, neutrophils = 1.5 x 109/L,
platelets = 80 x 109/L, hemoglobin = 90g/L;
2. International Standardized ratio (INR) and activated partial thromboplastin time
(APTT) =1.5× upper limit of normal (ULN);
3. Liver function: serum total bilirubin = 2 x ULN; ALT/AST = 2 x ULN; Serum albumin
=28g/L;
4. Renal function: serum creatinine = 1.5 x ULN or eGFR=60%, creatinine clearance
(CCr) =60mL/min; To rule out urinary system infection, urine routine showed urine
protein < 2+, =2+ patients should be collected 24 hours of urine protein volume <
1g;
5. Normal cardiac function with left ventricular ejection fraction (LVEF)=50% as
measured by two-dimensional echocardiography;
Fertile male or female patients volunteered to use effective contraceptive methods, such as
double barrier methods, condoms, oral or injectable contraceptives, and Iuds, during the
study period and within 6 months of the last study medication. All female patients will be
considered fertile unless they have undergone natural menopause, artificial menopause, or
sterilization (such as hysterectomy, bilateral adnexectomy, or irradiation of radioactive
ovaries).
Exclusion Criteria:
1. Participated in clinical trials of other anti-tumor drugs within 4 weeks before
enrollment;
2. Patients with a history of TACE treatment and who had previously received any immune
or targeted therapy were excluded; Patients with a history of hepatectomy,
postoperative recurrence, and no systemic therapy were included
3. The investigators determined that liver metastases accounted for 90% or more of the
total liver volume;
4. Patients who have previously received an organ transplant or are planning an organ
transplant;
5. Patients with obstructive jaundice but yellowing is not as expected;
6. Have had other malignancies within the past 5 years, except basal cell or squamous
cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
7. Patients who have had or are currently having any brain metastases;
8. Other strong inducers or suppressors of CYP3A4 were taken within 2 weeks prior to the
first study;
9. Received any surgery (except biopsy) or invasive treatment or operation within 4 weeks
before enrollment, and the surgical incision was not completely healed (except
intravenous catheterization, puncture drainage, etc.);
10. Electrolyte abnormalities identified by the investigator as clinically significant;
11. The patient currently has medically uncontrolled hypertension, defined as: systolic
blood pressure =140 mmHg and/or diastolic blood pressure =90 mmHg;
12. Urine routine indicated urinary protein =2+, and 24-hour urinary protein volume >
1.0g;
13. Patients whose tumors are judged by the investigators to be at high risk of invading
vital blood vessels and causing fatal massive bleeding during the follow-up study;
14. Patients with evidence or history of significant bleeding tendency within 3 months
prior to enrollment (bleeding within 3 months > 30 mL, hematemesis, stool, stool
blood), hemoptysis (within 4 weeks > 5 mL fresh blood); People with a history of
inherited or acquired bleeding or coagulation disorders. There were clinically
significant bleeding symptoms or definite bleeding tendencies within 3 months prior to
enrollment, such as gastrointestinal bleeding and hemorrhagic gastric ulcer;
15. Clinically significant cardiovascular disease, including but not limited to acute
myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass
grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Grades
for Congestive Heart Failure > Level 2; Ventricular arrhythmias requiring medical
treatment; Electrocardiogram (ECG) showed QT c interval =480 ms;
16. Active or uncontrolled severe infection (=CTCAE grade 2 infection);
17. Unmitigated toxicity higher than CTCAE grade 2 due to any previous anticancer therapy,
excluding alopecia, lymphocytopenia, and oxaliplatin grade =2 neurotoxicity;
18. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
19. Any other medical condition, clinically significant metabolic abnormality, physical
abnormality or laboratory abnormality, which, in the investigator's judgment,
reasonably suspects that the patient has a medical condition or condition that is not
suitable for the use of the investigational drug (such as having seizures and
requiring treatment), or which would affect the interpretation of the study results or
place the patient at high risk;
20. Known human immunodeficiency virus (HIV) infection; Known history of clinically
significant liver disease, including viral hepatitis [Known hepatitis B virus (HBV)
carriers must rule out active HBV infection, i.e., positive HBV DNA (>1×104 copies
/mL or > 2000 IU/ml); known hepatitis C virus infection (HCV) and HCV RNA positive
(>1×103 copies /mL), or other hepatitis, cirrhosis;
21. The presence of 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, pituitaritis, hyperthyroidism, etc.);
22. Known allergic reactions to other monoclonal antibodies or to any component of
solvatinib;
According to the investigators' judgment, the patients had other factors that might affect
the study results or lead to the forced termination of the study, such as alcoholism, drug
abuse, other serious diseases (including mental illness) requiring combined treatment,
serious laboratory abnormalities, and family or social factors that would affect the safety
of the patients.
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