| Eligibility |
Inclusion Criteria:
Subjects must meet all of the following conditions for enrollment:
1. subjects voluntarily enrolled in this study and signed an informed consent form, with
good compliance and cooperation with follow-up;
2. patients with unresectable focally advanced or metastatic pancreatic cancer diagnosed
by pathological histology or cytology
3. age between 18 and 75 years (both 18 and 75 years), male or female
4. ECOG score: 0-1; expected survival = 12 weeks;
5. have progressed after receiving at least one prior systemic therapy for locally
progressive or metastatic pancreatic cancer (including patients on first- or
second-line regimens containing 5-FU)
6. have at least one measurable lesion (according to RECIST 1.1 criteria); = 10 mm in
diameter as accurately measured by magnetic resonance imaging (MRI) enhancement or
computed tomography (CT) enhancement, and at least 20 mm in diameter as determined by
conventional CT scan
7. no serious organic diseases of the heart, lungs, brain and other organs;
8. essentially normal function of major organs and bone marrow:
1. routine blood (no blood transfusion, no granulocyte colony-stimulating factor
[G-CSF], no drug correction within 14 days prior to screening): leukocytes = 4.0
x 109/L, neutrophils = 1.5 x 109/L, platelets = 80 x 109/L, hemoglobin = 90 g/L;
2. International normalized ratio (INR) and activated partial thromboplastin time
(APTT ) = 1.5 x upper limit of normal (ULN);
3. liver function (no albumin transfusion within 14 days prior to screening): serum
total bilirubin = 1.5 x ULN, ALT/AST = 3 x ULN, and serum total bilirubin = 1.5 x
ULN after internal/external drainage for obstructive jaundice;
4. Renal function: serum creatinine = 1.5 x ULN, creatinine clearance (CCr) = 50
mL/min;
5. normal cardiac function, two-dimensional cardiac ultrasound detection of left
ventricular ejection fraction (LVEF ) = 50%; New York Heart Association (NYHA)
classification <3.
9. Male or female patients of childbearing potential voluntarily use an effective
contraceptive method such as a double barrier method, condom, oral or injectable
contraceptive medication, IUD, etc. during the study period and within 6 months of the
last study dose. All female patients will be considered fertile unless the female
patient is spontaneously menopausal, has undergone artificial menopause, or has been
sterilized.
Exclusion Criteria:
1. participation in other antitumor drug clinical trials within 4 weeks prior to
enrollment, including: interventional, chemotherapy, bioimmunotherapy, targeted
therapy, etc;
2. previous treatment with a previous vascular endothelial growth factor (VEGFR)
inhibitor or previous treatment with an immune checkpoint inhibitor, and previous
treatment with tegeo;
3. other malignancies within the past 5 years, except for basal or squamous cell
carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix
4. patients who have developed any brain metastases or are currently developing brain
metastases
5. with liver metastases representing 50% or more of the total liver volume as determined
by the investigator
6. have undergone any surgery (other than biopsy) or invasive treatment or operation
within 4 weeks prior to enrollment and the surgical incision has not fully healed
(except for intravenous placement, puncture drainage, internal/external drainage
procedures for obstructive jaundice, etc.)
7. have received local antitumor therapy such as hepatic artery interventional
embolization, cryoablation of liver metastases or radiofrequency ablation within 4
weeks prior to enrollment;
8. clinically significant electrolyte abnormalities in the judgment of the investigator;
9. the patient has current hypertension that is not controlled by medication, specified
as: systolic blood pressure = 140 mmHg and/or diastolic blood pressure = 90 mmHg
10. urine routine suggestive of urine protein = 2+ and 24-hour urine protein amount > 1.0
g
11. patients whose tumors are judged by the investigator to be at high risk of invading
important blood vessels and causing fatal hemorrhage during the follow-up study;
12. patients with evidence or history of significant bleeding tendency within 3 months
prior to enrollment (bleeding >30 mL within 3 months with vomiting, black feces, blood
in stool), hemoptysis (>5 mL of fresh blood within 4 weeks); those with a history of
hereditary or acquired bleeding disorders or coagulation disorders, who have had
clinically significant bleeding symptoms within 3 months or have a clear bleeding
tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcers, etc;
13. clinically significant cardiovascular disease, including but not limited to acute
myocardial infarction, severe/unstable angina, or coronary artery bypass grafting
within 6 months prior to enrollment; congestive heart failure New York Heart
Association (NYHA) class >2; ventricular arrhythmias requiring pharmacologic
treatment; and electrocardiogram (ECG) showing QT c interval =480 ms;
14. active or uncontrolled serious infection (= CTCAE grade 2 infection);
15. unremitting toxic reactions above CTCAE grade 2 due to any prior anticancer therapy,
excluding alopecia, lymphopenia and neurotoxicity = grade 2 due to oxaliplatin;
16. women who are pregnant (positive pregnancy test prior to dosing) or breastfeeding
17. any other disease with a clinically significant metabolic abnormality, physical
examination abnormality or laboratory test abnormality that, in the judgment of the
investigator, gives reason to suspect that the patient has a disease or condition that
is inappropriate for the use of the study drug (e.g., has seizures and requires
treatment) or that would affect the interpretation of the study results or place the
patient at high risk
18. known human immunodeficiency virus (HIV) infection; known history of clinically
significant liver disease, including viral hepatitis [known hepatitis B virus (HBV)
carriers must be excluded from active HBV infection, i.e., positive HBV DNA (>1×104
copies/mL or >2000 IU/ml); known hepatitis C virus infection (HCV) with HCV RNA
positive (>1×103 copies/mL), or other hepatitis, cirrhosis];
19. persons with any active, known or suspected autoimmune disease (including but not
limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, enterocolitis, multiple sclerosis, vasculitis,
glomerulonephritis, uveitis, pituitary inflammation, hyperthyroidism, etc.)
20. those who are allergic or suspected to be allergic to the study drug or similar drugs
21. Patients who, in the judgment of the investigator, have other factors that could
affect the outcome of the study or force the termination of this study midway, such as
alcoholism, drug abuse, other serious illnesses (including psychiatric illnesses)
requiring comorbid treatment, serious laboratory test abnormalities, accompanied by
family or social factors that would affect the safety of the patient.
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