Advanced Malignant Solid Tumors
Conditions
Interventions
100mg fixed dose group:100 mg fixed dose group
200mg fixed dose group:200 mg fixed dose group
400mg fixed dose group:400 mg fixed dose group
600mg fixed dose group:600 mg fixed dose group
800mg fixed dose group:800 mg fixed dose group
Sponsors
Shanghai Pulmonary Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18~75 years old (including the threshold), gender unlimited; 2. Patients with locally advanced or metastatic solid tumors confirmed by histology or cytology fail to receive standard treatment, or there is no standard treatment plan, or standard treatment is not applicable at this stage; 3. The expected survival time is more than 3 months; 4. According to RECIST version 1.1, there is at least one assessable tumor focus; 5. The score of physical fitness (ECOG PS) of the Eastern Cancer Cooperation Group in the United States is 0-1; 6. Patients with sufficient organ function: a) Blood system (no blood transfusion or hematopoietic stimulating factor treatment within 14 days before the first administration): Absolute value of neutrophils (ANC) = 1.5 ×10^9/L Platelet (PLT) = 75 ×10^9/L Hemoglobin (HB) = 85g/L; b) Liver function: Total bilirubin (TBIL) = 1.5 × Upper limit of normal value (ULN) (TBIL = 2.5 is required for patients with liver cancer × ULN, Child-Pugh grade A or grade B with score = 7); Alanine aminotransferase (ALT), aspartate aminotransferase (AST) = 3 × ULN (liver cancer or liver metastasis patients, AST and ALT = 5 × ULN) c) Renal function: Serum creatinine (Cr) = 1.5 × ULN or creatinine clearance rate (Ccr) = 50ml/min/1.73m^2 (Cockcroft-Gault formula, only creatinine>1.5 × ULN) d) Coagulation function: Activated partial activated thrombin time (APTT) = 1.5 × ULN International normalized ratio (INR) = 1.5 × ULN 7. Qualified patients with fertility (male and female) must agree to use reliable contraceptive methods (hormone or barrier method or abstinence) with their partners during the trial and at least 90 days after the last medication; Blood pregnancy test of female subjects of childbearing age within 7 days before the first use of drugs(ß- HCG) must be negative; 8. Subjects must give informed consent to the study before the test and voluntarily sign a written informed consent form.
Exclusion criteria
Exclusion criteria: 1. Patients have received chemotherapy, radiotherapy, biotherapy, targeted therapy, endocrine therapy, immunotherapy and other anti-tumor drugs within 4 weeks before the first administration, with the exception of the following: a) Nitrosourea or mitomycin C is within 6 weeks before the first use of the study drug; b) Oral fluorouracil and small-molecule targeted drugs are 2 weeks before the first use of the study drug or within 5 half-lives of the drug (whichever is shorter); c) Traditional Chinese medicine with anti-tumor indications is within 2 weeks before the first use of the study drug; d) Palliative radiotherapy (= 2 weeks before the first administration) and ongoing bisphosphonate treatment outside the target focus are allowed; 2. Patients have received systemic glucocorticoid (prednisone>10mg/day or equivalent dose of the same drug) or other immunosuppressive drugs within 14 days before the first administration; Except for the following: a) Use local, ocular, intraarticular, intranasal and inhaled glucocorticoids for treatment; b) Short-term use of glucocorticoids for preventive treatment (such as prevention of contrast agent allergy); 3. Patients who have received other unlisted clinical research drugs or treatment within 4 weeks before the first administration; 4. Major organ surgery (excluding puncture biopsy) or significant trauma has been performed within 4 weeks before the first administration, or selective surgery is required during the trial period; 5. Patients have used CYP3A4 potent inhibitor or CYP3A4 potent inducer within 7 days before the first use of the study drug (see Appendix 3 for details); 6. Patients who have received allogeneic hematopoietic stem cell transplantation or organ transplantation in the past; 7. The adverse reactions of previous anti-tumor treatment have not recovered to NCI-CTCAE v5.0 grade evaluation = 1 (except for the toxicity that the researcher judged to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, etc.); 8. Skin/decubitus ulcer, chronic leg ulcer, known active gastric ulcer or wound nonunion; 9. Patients have a history of severe allergy in the past, or allergic to any active or inactive components of the study drug; 10. Central nervous system metastasis or meningeal metastasis with clinical symptoms, or there is other evidence that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, and the researcher has judged that it is not suitable for enrollment; 11. Patients who have active infection and currently need systemic anti-infection treatment; 12. Patients have a history of immunodeficiency, including positive human immunodeficiency virus (HIV) test; 13. Active hepatitis B (HBsAg positive and HBV-DNA>1000 IU) (patients with hepatitis B who received prophylactic antiviral therapy other than interferon were enrolled); Hepatitis C virus infection; 14. Patients with interstitial lung disease; 15. Patients have a history of serious cardiovascular disease, including but not limited to: a) There are serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, and ?~? degree atrioventricular block; Corrected QTcF interval>450 ms for males and>470 ms for females; b) Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other cardiovascular and cerebrovascular events of grade 3 or above occurred within 6 months before the fir
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicity (DLT);Maximum tolerated dose (MTD);Recommended phase 2 dose (RP2D);Type, frequency and severity of treatment-emergent adverse event (TEAE) (evaluated according to NCI-CTCAE v5.0);Serious adverse event (SAE) and toxic reactions leading to permanent withdrawal;Changes in laboratory safety inspection results (classified according to NCI-CTCAE v5.0);Changes of vital signs and 12-lead electrocardiogram (ECG); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic indexes: area under the concentration time curve from time zero to time t (AUC0-t, AUC0 - 8), maximum concentration (Cmax), time to reach maximum drug concentration (Tmax), half life (T1/2), apparent volume of distribution (Vd/F), clearance (CL/F), etc;Best of response (BOR);Qbjective response rate (ORR);Progression-free survival (PFS);Disease control rate (DCR);Duration of response (DOR); | — |
Countries
China
Contacts
Public ContactZhou Caicun
Shanghai Pulmonary Hospital
Outcome results
None listed