Advanced Solid Tumor
Conditions
Brief summary
Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2#VEGFR-2#, Induces Transporter Pgp function in vitro. This study in patients with advanced cancer evaluated the effect of Apatinib on Transporter Pgp function by comparing the pharmacokinetics of Transporter Pgp-specific probe drugs in the presence and absence of Apatinib. The probes used Substrate Digoxin.
Interventions
DRUGApatinib Mesylate
Apatinib at a dosage of will be administered daily from on D5 through D16
DRUGDigoxin tablet
Digoxin at a dosage of 0.25mg will be administered at day 1 and day 12
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1\. Histologically or cytologically confirmed diagnosis of advanced solid tumors. 2. ECOG PS score: 0-1; 3. Expected survival ≥ 3 months; 4. Major organs must function normally, meeting the following criteria: 1. Hematology 1. HB≥100 g/L; 2. ANC≥1.5×109/L; 3. PLT≥90×109/L; 2. Blood biochemistry: 1. TBIL≤ 1.25×ULN; 2. ALT and AST≤2.5×ULN; 3. ALP≤2.5×ULN; 4. Serum Cr ≤ 1.5 × ULN or endogenous CrCl ≥ 60 mL/min (Cockcroft-Gault formula); 5. Albumin \> 30 g/L; 6. K+\>3.0mmol/L; 5. Able to understand and sign an informed consent form (ICF).
Exclusion criteria
1. Primary liver cancer; gastric cancer; 2. Active brain metastasis (medically uncontrolled), carcinomatous meningitis, spinal cord compression; 3. Presence of clinically symptomatic third space fluid; 4. Uncontrolled hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg despite optimal pharmacological treatment); 5. Uncontrolled clinically significant heart disease, including but not limited to the following: (1) \>2 NYHA 2 congestive heart failure; (2) left ventricular ejection fraction (LVEF) \< 50% (3) heart rate \<60 (4) Grade II or greater myocardial ischemia or myocardial infarction(5) QTc interval ≥ 450 ms in males and ≥ 470 ms in females; 6. Abnormal coagulation function; 7. Prior radiotherapy, systemic chemotherapy (\< 6 weeks if chemotherapy including nitrosoureas or mitomycin), hormone therapy, surgery or target therapy within 4 weeks before the study drug administration, or any unresolved AEs \> CTC-AE Grade 1; 8. History of psychotropic substance abuse, alcoholism or drug abuse; 9. Use of study drugs in other clinical trials within 4 weeks prior to the first dose； 10. Use of a potent CYP3A4 inhibitor or inducer within 2 weeks prior to the first dose; 11. Use of any prescription or over-the-counter medication, vitamin products or herbs within 2 weeks before taking the investigational drug; 12. Other factors that may lead to the termination of the participation in the study at the discretion of the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics parameter: Cmax of digoxin | through study completion, an average of 16 days | Peak Plasma Concentration (Cmax) of digoxin |
| Pharmacokinetics parameter: AUC of digoxin | through study completion, an average of 16 days | Area under the plasma concentration versus time curve (AUC) of digoxin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameters CL/F of digoxin | through study completion, an average of 16 days | Total body clearance for extravascular administration (CL/F) of digoxin |
| Pharmacokinetics parameter: Tmax of digoxin | through study completion, an average of 16 days | Time of maximum observed concentration (Tmax) of digoxin |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | through study completion, an average of 16 days | An adverse event is any untoward medical occurrence in a patient or clinical study participant criteria |
| Pharmacokinetics parameter: Vz/F of digoxin | through study completion, an average of 16 days | Volume of distribution (Vz/F) of digoxin |
| Pharmacokinetics parameter: T1/2 of digoxin | through study completion, an average of 16 days | Half time (T1/2) of digoxin |
Countries
China
Outcome results
None listed