Recurrent or advanced solid tumor
Conditions
Interventions
Experimental group:SYHA1813 oral solution
Sponsors
Beijing Tiantan Hospital Affiliated to Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subjects fully understand and voluntarily participate in this study and sign informed consent; 2. Aged >= 18 years, no gender limitation; 3. Recurrent or advanced solid tumors confirmed by histology or cytology, including but not limited to high-grade glioma (including glioma), brain metastases, kidney cancer, colorectal cancer, thyroid cancer, lung cancer, gastric cancer, tendon sheath Giant cell tumor, etc., disease progression under standard treatment, intolerance to standard treatment or lack of effective standard treatment; 4. The time between the end of the last anti-tumor treatment and the first administration of SYHA1813 meets the following time intervals: cytotoxic drugs, immunotherapy, macromolecular targeted drugs, biological therapy >= 4 weeks; oral small-molecule targeted drug therapy, anti-cancer traditional Chinese medicine or proprietary Chinese medicine Wait for >= 2 weeks or 5 half-lives of known drugs (whichever is longer); radiotherapy >= 4 weeks (palliative local radiotherapy for symptom relief >= 2 weeks); 5. KPS score of patients with central nervous system tumors >= 60 points; ECOG physical performance (PS) scores of patients with other solid tumors 0-2; 6. The expected survival time is >=12 weeks; 7. There is at least one measurable lesion in the baseline period (primary tumors of the central nervous system must meet the RANO standard, and other solid tumors must meet the RECIST1.1 standard); 8. The organ function level and related laboratory indicators must meet the following requirements: (1) Blood routine (no blood transfusion within 2 weeks): absolute neutrophil count (ANC) >=1.5 x 10^9/L; platelet count >=100 x 10^9/L; hemoglobin >= 90g/L; (2) Blood biochemistry: serum total bilirubin <= 1.5 times the upper limit of normal (ULN); AST/ALT <= 3 times ULN (if liver metastases, allow AST/ALT <= 5 times ULN); serum creatinine <= 1.5 times ULN; (3) Coagulation function: International normalized ratio (INR) or prothrombin time (PT) <= 1.5 times ULN, activated partial thrombin time (APTT) <= 1.5 times ULN; 9. The blood pregnancy test results of fertile women within 7 days before the first administration of SYHA1813 must be negative, and the female subjects are willing to take medically approved contraceptive measures during the trial and at least 3 months after the last administration of the test drug . Male subjects must agree to take medically approved contraceptive measures for at least 3 months from the beginning of the study to the last dose of SYHA1813.
Exclusion criteria
Exclusion criteria: 1. The previous history of anti-tumor and surgical treatment meets any of the following: (1) In the treatment period of other interventional clinical studies within 4 weeks before taking SYHA1813 for the first time; (2) Have received major surgery within 4 weeks before taking SYHA1813 for the first time; (3) Patients with glioma or brain metastases who have used glucocorticoid with an equivalent dose of more than 5 mg dexamethasone within 5 days before the first medication; (4) Bevacizumab has been used after brain metastasis of brain glioma or solid tumor. 2. The toxicity of previous anti-tumor treatments has not recovered (>=2), except for hair loss, pigmentation, and other adverse reactions judged by the investigator that do not affect the safety of the study medication. 3. Subjects with impaired cardiac function or clinically significant cardiovascular and cerebrovascular diseases, including but not limited to: (1) A history of myocardial infarction, congestive heart failure (NYHA grade III-IV), and unstable angina pectoris within 6 months; (2) Cerebrovascular accident occurred within 6 months (transient ischemic attack, lacunar infarction with no clinical significance can be included in the group); (3) Hypertension that cannot be controlled after medication (repeated blood pressure measurement at least 1 hour apart, and blood pressure value 150/90mmHg for two consecutive times); (4) Severe uncontrolled arrhythmia requiring medical treatment; (5) Electrocardiogram (ECG) examination, QTc interval>470 milliseconds (ms); (6) Left ventricular ejection fraction =2+, or 24-hour urine protein quantitative >= 1.0g/24h. 5. The subject has poorly healed wounds, ulcers or fractures. 6. Those who are receiving warfarin or other oral anticoagulants are allowed to use low-dose anticoagulants to maintain the patency of the central venous access or prevent deep vein thrombosis, and allow the therapeutic use of low molecular weight heparin. 7. Patients with a history of arterial thrombosis or deep vein thrombosis within 6 months, or with evidence of bleeding tendency or medical history within 2 months before enrollment, regardless of severity. 8. Subjects with dysphagia or known drug absorption disorders, including but not limited to: (1) Do not take drugs orally; (2) Have received surgery that affects the digestion or absorption of the gastrointestinal tract, including total gastrectomy, etc.; (3) A history of peptic ulcer within 6 months; (4) Severe diarrhea within 7 days before the first medication (CTCAE >= 2); (5) Malabsorption syndrome. 9. Patients with brain tumors that involve the brainstem or are at risk of severe or severe brain herniation. 10. Within 2 weeks before the first administration of SYHA1813, there is any uncontrollable active infection that prevents the subject from receiving the test drug (CTCAE >= grade 2). 11. Other serious systemic diseases, including but not limited to uncontrolled diabetes, kidney disease requiring dialysis, severe liver disease (Child-Pugh grade B or C), acute pancreatitis, etc. 12. Have a clear history of mental illness. 13. Human immunodeficiency virus (HIV) antibody positive; active hepatitis C, antibody positive and HCV RNA test positive; active hepatitis B, HBV DNA test for HBsAg positive, HBV DNA is higher than the upper limit of the normal value of the research center Need to be excluded. 14. A history of any other malignant tumors within 5 year
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity (DLT) DLT will be assessed according to NCICTCAE v5.0.;Maximum tolerated dose (MTD), MTD will be defined as the maximum dose level at which no more than 1 of 3 patients experience a DLT within cycle1 (28 days) of DLT observing period.;Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs) The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.;Phase II dose (RP2D); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) characteristics- Cmax;Pharmacokinetic (PK) characteristics- Tmax; Pharmacokinetic (PK) characteristics- AUC0-t; Pharmacokinetic (PK) characteristics- AUC0-8;Pharmacokinetic (PK) characteristics- t1/2; Pharmacokinetic (PK) characteristics- CL/F; Objective Response Rate (ORR); Disease control rate (DCR); Duration of response (DoR);Progression-free survival (PFS); Potential biomarkers; | — |
Countries
China
Contacts
Public ContactLi Wenbin
Beijing Tiantan Hospital Affiliated to Capital Medical University
Outcome results
None listed