Advanced solid tumor
Conditions
Interventions
Experimental group:Oral SC0191 piece
Sponsors
Sun Yat-Sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria (all the following criteria must be met): 1.For the dose escalating stag, histological or cytological diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available; 2.For the dose expansion stage, histological or cytological diagnosis of advanced/metastatic solid tumor that has progressed during or after standard treatment, and screened for defects of TP53, H3K36me3, or other DDR-associated genes; 3.Patients have at least one measurable lesion according to RECIST1.1 (in dose escalating stage, subjects have no measurable lesions but have evaluable lesions at the discretion of the treating physician are also allowed); 4.Subjects participate in the study voluntarily and have signed informed consent form; 5.Age >= 18 years old, = 3 months; 8.Patients must have normal organ and laboratory results as defined below: Absolute Neutrophils Count >= 1.5 x 10^9/L; Platelets >= 100 x 10^9/L; Hemoglobin >= 90g/L, no blood transfusion or hematopoietic stimulating factor therapy received within 14 days; Adequate Liver function as defined by: total serum bilirubin 50 mL/min; Fasting blood glucose = 2+, the 24-hour urine protein excretion must be < 3.5g/24h; 9.Women of childbearing potential must have a negative serume pregnancy test within 7 days prior to the first dose and agree to use adequate contraception prior to study entry and for at least 3 months (or at least 90 days) after the last dose.Male subjects must consent to adequate contraception prior to study entry and for at least 3 months (or at least 90 days) after the last dose.
Exclusion criteria
Exclusion criteria: Exclusion criteria (as long as one criterion is met): 1.Subjects received chemotherapy, radiotherapy, immunotherapy, endocrine therapy and other anti-tumor therapies within 3 weeks before the first administration, 6 weeks for Nitrosolurea or mitomycin C; five half-lives or 14 day for small molecule targeting agents(whichever is shorter), should also be excluded.); 2.Received another unmarketed investigational drug or treatment within 3 weeks prior to initial use of the investigational drug; 3.Had major organ surgery (excluding needle biopsy) or significant trauma within 3 weeks prior to the first use of the investigational drug, or requires elective surgery during the study period; 4.Received traditional Chinese medicine with anti-tumor effect within 2 weeks before the first use of the drug; 5.Received WEE1 inhibitor treatment before in the dose-escalating stage; Previous treatment with WEE1 inhibitors or other DDR-related inhibitors (e.g., PARP inhibitors) during the dose expansion phase; 6.The subject has not recovered to NCI CTCAE5.0 grade evaluation10mg prednisone (or equivalent drug) per day before enrollment; (3) Unstable CNS metastasis after the last local treatment or being stable less than 28 days before enrollment. 8.The presence of active infections requiring treatment; 9.Meeting the study center's criteria for active hepatitis B infection (HBV DNA>= 1000 copies or 200IU) or positive to human immunodeficiency virus (HIV) or hepatitis C antibody (inactive syphilis can be enrolled). 10.Heart function or disease meets one of the following conditions: -During the screening period, three 12-lead electrocardiogram (ECG) measurements will be carried out in the research center. According to QTC formula by the instruments in the center, the average values of three results for QTc > 470 ms; (1) Complete left bundle branch block, degree II or above atrioventricular block, rapid ventricular tachycardia (including frequent premature ventricular beats), torsades de pointes; (2) Any risk factors that prolong QTC interval, such as uncorrected hypokalemia, hereditary long QT syndrome, taking drugs that prolong QTC interval (mainly class Ia, Ic and III antiarrhythmic agents); (3) Congestive heart failure: New York Heart Association (NYHA) >= grade 3; 11.Active digestive disease, or had major gastrointestinal surgery, or malabsorption syndrome, or other conditions that may impair the absorption of SC0191 tablets (such as ulcerative lesions, uncontrollable nausea, vomiting, diarrhea, malabsorption syndrome, and enteroctomies); 12.History of interstitial lung disease or drug-induced interstitial lung disease, radiation pneumonia requiring hormone therapy; 13.History of pancreatitis; 14.Subjects who have received a strong CYP3A inhibitor (Amprenavir, Atazanavir, Boceprevir, Clarithromycin, Conivaptan, Delavirdine, Diltiazem, Erythromycin, Fosamprenavir, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mibefradil, Miconazole, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Saqui
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity (DLT); | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety endpoints;Efficay end point: ORR, PFS, DOR, DCR, etc.;Pharmacokinetic indicators:AUC0-last, AUC(0-24h), AUC (0-8), Cmax, tmax, t1/2, Vd, CL/F, Ctrough, Accumulate index Rac, etc.;Pharmacodynamics index: ?H2AX, P-CDK1/2, dNTP (only during the dose expansion stage); | — |
Countries
China
Contacts
Public ContactZhang Li
Cancer Center of Sun Yat-Sen University
Outcome results
None listed