Advanced solid tumor
Conditions
Interventions
Dose increasing group (2.5mg/m2):Dosing every 3 weeks (the dose and frequency of dosing in the next dose group can be adjusted based on safety and PK data
Additional dose groups may be added as appropriate). Accelerated titration and the traditional "3+3" method were used for dose escalation.
Dose increasing group (7.5mg/m2):Dosing every 3 weeks (the dose and frequency of dosing in the next dose group can be adjusted based on safety and PK data
Dose increasing group (15mg/m2):Dosing every 3 weeks (the dose and frequency of dosing in the next dose group can be adjusted based on safety and PK data
Dose increasing group (25mg/m2):Dosing every 3 weeks (the dose and frequency of dosing in the next dose group can be adjusted based on safety and PK data
Dose increasing group (35mg/m2):Dosing every 3 weeks (the dose and frequency of dosing in the next dose group can be adjusted based on safety and PK data
Dose increasing group (45mg/m2): Dosing every 3 weeks (the dose and frequency of dosing in the next dose group can be adjusted based on safety and PK data
Dose extension Group (SAK2001):SA
Sponsors
The First Affiliated Hospital, Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria: (1) Written informed consent (ICF) must be signed before any research-specific procedure can be performed. (2) Age 18-75 (including upper and lower limits). (3) Subjects with advanced solid tumors confirmed histologically or cytologically by standard treatment failure or intolerance or relapse after treatment. (4) There was at least one measurable (increasing/expanding) or evaluable (increasing) tumor lesion (RECISTv 1.1 efficacy evaluation criteria). (5) The physical status score of the Eastern Oncology Collaboration Group (ECOG) was less than 1 point. (6) Expected survival =3 months. (7) Good organ function (no blood transfusion, blood products, or blood cell growth factors such as granulocyte colony stimulating factor within 2 weeks), including: Blood routine: neutrophil count (ANC)=1.5×109 /L, platelet count (PLT)=90×109/L, and hemoglobin (Hb) =90 g/L. Renal function: Serum creatinine =1.5 times the upper limit of normal (ULN) or calculated muscle Anhydride clearance (Ccr) >60 mL/min. Ccr formula: male Ccr = [(140 - years of age) by weight (kg)] / [0.818 x Scr (mu mol/L)], women Ccr = 0.85 x [(140 - age) by weight (kg)] / [0.818 x Scr (mu mol/L)]. Liver function: total bilirubin (TBIL) =1.5ULN, aspartate transaminase (AST) =2.5 times ULN, alanine transaminase (ALT) =2.5 times ULN (if liver metastasis exists during screening: aspartate transaminase (AST) =5 times ULN, alanine transaminase (ALT) =5 times ULN). Coagulation function: activated partial thromboplastin time (aPTT) =1.5 times ULN, coagulation The proenzyme time (PT) is =1.5 ULN, and the International Normalized ratio (INR) is =1.5 ULN. (8) Women of reproductive age and all male subjects agree to use adequate contraceptive methods (such as condoms and intrauterine devices) during the trial period and for at least 6 months after the end of the study treatment; Blood human chorionic gonadotropin (hCG) pregnancy test results must be negative for female subjects of childbearing age within 7 days prior to first receiving the study drug; All male subjects were not allowed to donate sperm during the trial and for at least six months after the end of the study treatment. (9) Willingness and ability to comply with clinical protocol (as determined by the investigator).
Exclusion criteria
Exclusion criteria: Subjects will not be enrolled in this study if they meet any of the following criteria: (1) lactating women. (2) Subjects with clinical symptoms of brain metastasis, spinal cord compression, cancerous meningitis, or other evidence of uncontrolled brain or spinal cord metastasis. (3) = grade 2 peripheral neuropathy (NCI CTCAE v5.0). (4) Subjects with severe epilepsy or dementia who have a history of severe central nervous system or psychiatric disorders requiring medication (such as sterol or antiepileptic drugs). (5) Severe cardiovascular disease, including but not limited to: unstable angina, symptomatic coronary artery disease, severe arrhythmia, myocardial infarction, baseline left ventricular ejection fraction less than 50%, heart failure, New York College of Cardiology (NYHA) grade II or above; Clinically significant baseline ECG QTc interval prolongation (male >450 ms, female >470 ms) and other unstable heart disease. (6) uncontrolled, active and severe infections (those requiring systemic anti-infective therapy according to the NCI CTCAE v5.0 level >2, or those with unexplained pre-administration body temperature >38?). (7) Having symptoms or signs of other serious diseases, including but not limited to: End-stage organ failure, other major chronic diseases other than cancer (such as end-stage diabetes, grade IV hypertension, severe coagulation abnormalities, stroke or transient ischemic attack, pulmonary embolism, or non-catheter-associated deep vein thrombosis, active autoimmune disease within 6 months prior to inclusion in this trial). (8) A history of other malignancies (other than cured cervical cancer or basal cell carcinoma of the skin) within 5 years. (9) Previous docetaxel palliative chemotherapy (adjuvant therapy if docetaxel treatment, recurrence time within 6 months after the last dose) or other conditions in which docetaxel monotherapy was not considered appropriate by the investigator. (10) A history of severe allergy to excipients of the investigational drug (= 3 according to NCI CTCAE v5.0 level) Study drug excipients included: vitamin E, egg yolk lecithin, medium chain triglyceride, sucrose. * In the expansion phase, subjects with severe allergy to Taxote@ excipients including Tine80 and ethanol for injection are not recommended to be included in the positive control group. (11) Radiotherapy, chemotherapy, surgery (other than diagnostic biopsy), immunotherapy or other antitumor (such as biologics or hormones) therapy within 4 weeks prior to initial administration, nitroso-urea or mitomycin therapy within 6 weeks, Received oral fluorouracil, small-molecule targeted drugs, and traditional Chinese medicine with anti-tumor indications within 2 weeks or within 5 half-lives of known drugs (depending on the duration), and the adverse reactions of previous anti-tumor treatment could not be recovered to NCI CTCAE v5.0 level =1 (except for toxicity without safety risk as determined by researchers, such as hair loss). (12) Received any investigational drug within 4 weeks prior to initial dosing (if it is determined that the 5 half-life of the investigational drug previously used by the subject is <4 weeks, 5 half-lives may also be used). (13) Received drugs with significant effects on the CYP3A metabolic enzyme pathway within 2 weeks prior to initial administration (including but not limited to: Cyclosporine, Terphenadine, ketoconazole, Miconazole, Itraconazole, Voriconazole, erythromycin, acetonamycin, Telyci
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Security. MTD/RP2D; Safety and tolerance, including: occurrence of DLT, AE, SAE, laboratory tests, electrocardiogram, vital signs, physical examination, ECOG score, etc.; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK characteristics. PK parameters include but are not limited to: Area under drug time curve (AUCinf, AUC0-t), maximum concentration (Cmax), peak time (Tmax), elimination rate constant (Kel), half-life (t1/2), apparent clearance rate (CL), apparent volume of distribution (Vz), average residence time (MRTinf), etc.;Curative effect. Validity parameters include: ORR, DCR, DOR, PFS.; | — |
Countries
China
Contacts
Public ContactLiu Jian
The First Affiliated Hospital, Zhejiang University School of Medicine
Outcome results
None listed