| Eligibility |
Inclusion Criteria:
Subjects must meet all of the following criteria to enter the study:
1. Age: 18-70 years old (Include both values);
2. Patients with histopathologically or cytologically confirmed advanced solid
tumor(except primary gastrointestinal tumors or metastatic gastrointestinal tumors and
primary hepatocellular tumors) , not necessary to have measurable lesions;
3. The standard systemic treatment plan for tumors is ineffective, or intolerable, or
there is no recurrence and metastasis after adjuvant chemotherapy and radiotherapy
after surgery;
4. ECOG PS score: 0-1;
5. Expected survival = 3 months;
6. Adverse reactions caused by the subject receiving other treatments have recovered
(recovered to = grade 1 according to NCI-CTCAE 5.0, except for hair loss), more than 4
weeks after receiving radiotherapy or surgery or receiving other cytotoxic drugs or
cell growth inhibitor.
7. Major organs must function normally, meeting the following criteria:
I. Haematology (no blood transfusion or blood products within the last 14 days, not
corrected with G-CSF or other hematopoietic colony-stimulating factors):
1. HB=100 g/L;
2. ANC=1.5×109/L;
3. PLT=90×109/L;
II. Blood biochemistry:
1. TBIL= 1.25×ULN;
2. ALT and AST=2.5×ULN;
3. ALP=2.5×ULN;
4. Serum Cr = 1.5 × ULN or endogenous CrCl = 60 mL/min (Cockcroft-Gault formula);
5. Albumin > 30 g/L;
III. Urine protein inspection:
a. Urinary routines suggest that urine protein <++. If urinary protein = ++, the
quantification of urinary protein in 24 hours should be =1.5 g;
8. Agree to abstinence or take effective contraception during the study and for at least
8 weeks after the last study drug administration
9. Sign the ICF voluntarily, have good compliance, corporate with follow-up visits, and
follow the study requirements.
Exclusion Criteria:
Subjects meeting any one of the followings will be excluded in this study:
1. Patients with gastrointestinal diseases that affect the use or absorption of drugs,
such as gastric cancer or intestinal cancer, unable to swallow, chronic diarrhea,
intestinal obstruction, large stomach or total gastrectomy, or within 6 months before
the first medication Patients with abdominal fistula, gastrointestinal perforation or
abdominal abscess;
2. Active (without medical control) brain metastases, cancerous meningitis, spinal cord
compression patients, or imaging CT or MRI examination at screening to find diseases
of the brain or pia mater
3. Presence of clinically symptomatic third space fluid (e.g. large pleural fluid or
ascites) that cannot be controlled by drainage or other methods;
4. Patients with hypertension, or patients with a history of hypertension
5. Patients with NYHA Class III-IV cardiac insufficiency or left ventricular ejection
fraction (LVEF) < 50% by echocardiography; uncontrolled arrhythmias (QTc interval =
450 ms in males and = 470 ms in females);
6. During the study period, patients should be used drugs that may lead to prolonged QTc
interval (such as antiarrhythmic drugs, quinidine, disopyramide, procainamide,
sotalol, amiodarone, etc.)
7. Patients with abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN
+ 4 s or APTT > 1.5 ULN)
8. Patients with clinically significant bleeding or clear bleeding tendency within 3
months prior to the first dose, such as coughing up blood, hemoptysis, GI bleeding,
hemorrhagic gastric ulcer, or baseline fecal occult blood (FOB) ++ and above.
Gastroscopy is required for patients with FOB (+) and no surgical resection of primary
gastric tumor. In case of ulcerative gastric cancer, patients are not enrolled due to
a risk of acute gastrointestinal hemorrhage;
9. Events of arterial/venous thrombosis within 6 months prior to the first dose, such as
cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage,
brain infarction), deep vein thrombosis, and pulmonary embolism;
10. Known hereditary or acquired hemorrhage and thrombophilia (such as hemophilia,
coagulopathy, thrombocytopenia, hypersplenism, etc.);
11. Patients treated with anticoagulants or vitamin K antagonists such as warfarin,
heparin or similar drugs;
12. Have undergone major surgery or with severe traumatic injury, fracture, or ulcer
within 4 weeks prior to the first dose; There is no previous wound healing.
13. Use of study drugs in other clinical trials within 4 weeks prior to the first dose;
14. Drugs that is CYP3A inhibitor, or the transporter BCRP or MATE1 inhibitor, or drugs
that affect gastric acid secretion, or Chinese herbal medicines within 2 weeks before
the first dose; use the drug that is metabolic enzyme CYP3A inducer within 4 weeks
before the first dose
15. Infectious disease screening (hepatitis B virus surface antigen, hepatitis C virus
antibody, Treponema pallidum antibody and human immunodeficiency virus antibody)
positive
16. History of immunodeficiency, with acquired, congenital immunodeficiency disease, or
history of organ transplantation
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