Small Cell Lung Cancer
Conditions
Interventions
Ib 16mg:HTMC0435 tablets 8 mg, bid, continued daily oral administration, each dose group combined with etoposide 75 mg/m^2, intravenous infusion for about 60 minutes, for 3 days (day 1 to day 3 of eac
Ib 24mg:HTMC0435 tablets 12 mg, bid, continuous oral administration every day, each dose group combined with etoposide 75 mg/m^2, intravenous infusion for about 60 minutes, for 3 days (day 1 to day 3
Stage II:The preliminary efficacy of the combination in patients with extensive-stage small cell lung cancer was investigated at the dose of HTMC0435 tablets in combination with cisplatin/carboplatin
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age>=18 years old=3 months; 8. Among the pre-enrollment examination indicators, there was no serious hematopoietic dysfunction, and the heart, lung, liver, and kidney functions were basically normal: a) bone marrow reserve (no blood transfusion or hematopoietic stimulating factor therapy within 14 days): hemoglobin>=9 g/dL, neutrophil >=1500/mm^3 and platelets>=75000/mm^3; b) Coagulation function: the international normalized ratio (INR) and activated partial thromboplastin time (APTT) were both =50ml/min (calculated according to the Cockcroft-Gault formula); d) Liver function: total bilirubin (TBIL) =50%; 9. Understand and voluntarily sign the written informed consent form (ICF), and have the willingness and ability to complete regular visits, treatment plans, laboratory tests and other trial processes.
Exclusion criteria
Exclusion criteria: 1.Patients with histologically or cytologically confirmed transformed SCLC or combined SCLC. 2.Prior treatment with any poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor. 3.Medical contraindications to etoposide or platinum-based chemotherapy (carboplatin or cisplatin). 4.Previous diagnosed or current compressive myelopathy. 5.Pleural, pericardial, or abdominal effusion that cannot be controlled after previous treatment or requires repeated drainage (once a month or more frequently). 6.Received treatment with cranial irradiation =4 weeks or bone irradiation =2 weeks prior to the first dose of HTMC0435; received treatment with Chinese medicine with anti-tumor indications =2 weeks prior to the first dose of HTMC0435; received any other study drug or participated in other clinical studies for therapeutic purposes =4 weeks prior to the first dose of HTMC0435. 7.Any unrecovered adverse events of prior therapy >CTCAE 5.0 Grade 1 (except for toxicity that the investigators judged to have no safety risks, such as alopecia). 8.Currently suffering from interstitial lung disease =CTCAE Grade 2. 9.Major surgery (excluding needle biopsy) within 4 weeks before the first dose of HTMC0435. 10.Past surgical history or severe gastrointestinal diseases that the investigator believes may affect the absorption, distribution or metabolism of the study drug, such as dysphagia, active gastric ulcer, ulcerative colitis, Crohn's disease, ileus, etc. 11.History of severe cardiovascular and cerebrovascular diseases, including but not limited to: uncontrolled high blood pressure; severe heart rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, ?-? atrioventricular block, etc.; acute coronary syndrome, congestive heart failure, stroke, or other grade 3 or higher cardiovascular events occurred within 6 months before the first dose of HTMC0435. 12.Received CYP3A4 potent inhibitors or inducers within 7 days before the first dose of HTMC0435 or need to use these medications during the study. 13.Symptomatic brain metastases or meningeal metastases or other evidence of uncontrolled central nervous system or meningeal metastases in patients who were judged by the investigators to be unsuitable for inclusion. 14.Active infectious diseases which need systemic anti-infection treatment. 15.Hepatitis B surface antigen (HBsAg) positive with hepatitis B virus (HBV) -DNA >1000 copies/mL or >200 IU/mL; hepatitis C virus antibody (HCV-Ab) positive. 16.Human immunodeficiency virus antibody (HIV-Ab) positive. 17.Previous or current diagnosis of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). 18.Women who are pregnant or breastfeeding; women/men who are planning to have a child; women/men who refuse to use medically approved contraceptive measures for contraception during the study treatment and within 6 months after the end of the study. 19.Serious psychological or mental abnormalities that may affect compliance of patients in this study. 20.Current alcohol or drug abusers. 21.Judgment by the investigator that the patient is not suitable for this study due to other conditions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity;Adverse event;Maximum tolerated dose;Recommended phase 2 dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic measures - the area under the concentration-time curve from dosing (time 0) to time infinity (AUC 0-inf) ;Pharmacokinetic measures - the area under the concentration-time curve from dosing (time 0) to time t (AUC 0-t);Pharmacokinetic measures - apparent clearance rate (CL/F) ;Pharmacokinetic measures - maximum plasma concentrations (Cmax);Pharmacokinetic measures - time to reach Cmax (Tmax) ;Pharmacokinetic measures - trough concentrations at steady state (Css, min);Pharmacokinetic measures - peak concentrations at steady state (Css, max) ;Pharmacokinetic measures - accumulation ratio (Rac);Pharmacokinetic measures - terminal plasma half-life (T1/2);Pharmacokinetic measures - apparent volume of distribution during terminal phase (Vz/F) ;Progression-free survival (PFS);Objective response rate (ORR);Disease control rate (DCR);Duration of response (DOR);Overall survival (OS); | — |
Countries
China
Contacts
Public ContactXingya Li
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed