Solid Tumor, Adult
Conditions
Keywords
Gastric Cancer, VEGFR inhibitor
Brief summary
The purpose of this China Phase I bridging study is to to evaluate the safety, tolerability and pharmacokinetic profile of telatinib in China patients with advanced solid tumor
Detailed description
This is an open-label, nonrandomized, phase I, escalating dose study to evaluate the safety, tolerability and pharmacokinetic profile of telatinib. . This study is comprised of two stages. The 1st stage follows the traditional 3+3 dose-escalation design. Telatinib mesylate tablets will be administrated orally to patient twice daily at a starting dose of 600 mg bid. Patients will be successively enrolled into three cohorts from low-dose to high-dose (600 mg bid, 900 mg bid, and 1200 mg bid). For each cohort, patient will be first enrolled for single-dose PK and safety observation. After one-day interval, patient will then be resumed for a 21-day continuous treatment to assess safety, tolerability and PK profile with multiple dosing. The dose-limiting toxicity (DLT) observation period will be 23 days, starting from the first day of single dosing till the end of the 21-day continuous treatment. If first 3 subjects at a dose level complete a cohort without experiencing any DLT, subjects for the next higher cohort will be recruited. If 1 of the first 3 subjects experiences DLT, then up to three additional subjects (total up to six subjects) will enrolled at that dose level. If more than 2 patients at a dose level experienced DLT, dose escalation will be halted. And the dose level will be declared the toxic dose. The MTD is defined as the previous (lower dose) dose level. If MTD is not observed even at 1200 mg bid, dose-escalation will not be continued.
Interventions
DRUGTelatinib Mesylate
Telatinib mesylate tablets will be administrated twice a day orally
Sponsors
Fountain Medical Development Co., Ltd.
Taizhou EOC Pharma Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is comprised of two stages. The 1st stage will follow the traditional 3+3 dose-escalation design in patients with advanced solid tumor The 2nd phase will be conduced in Gastric cancer patients, primarily for PK data collection
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in the study patients should fulfil the following criteria: 1. Provision of informed consent prior to any study specific procedures. 2. ≥ 18 and ≤ 70 years of age 3. For the 1st phase: histological or cytological confirmed solid malignant tumors in advanced stage, standard regimen failed or intolerable, or no standard regimen available For the 2nd phase: histological or cytological confirmed gastric cancer in advanced stage. 4. ECOG performance status of 0-1 5. Life expectancy of more than 12 weeks 6. Patients must have adequate organ and bone marrow function as defined by the following laboratory results. 1. Neutrophil \> 1.5 × 10\^9/L 2. Platelets \>100 × 10\^9/L 3. Alkaline phosphatase ≤2 times the upper limit of normal (ULN) 4. Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (APPT) \< 1.5 times ULN 5. Hemoglobin ≥ 9 g/dL. 6. Creatinine ≤ 1.5 times the upper limit of normal (ULN) for the institution or Creatinine clearance ≥ 60 ml/min 7. Total bilirubin ≤ 1.5 times ULN 8. Aspartate transaminases (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 2.5 times ULN. In HCC patients, those two values should be \< 5 times ULN 9. Urine protein \<2+; if urine protein ≥ 2+, 24-hour urine protein quantity must ≤ 1g 7. Patients must be able to swallow tablets, not spit out the drug, and without malabsorption 8. Patients must NOT suffer from medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, or assessment of response or anticipated toxicities.
Exclusion criteria
Patients should NOT enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity, incidence of treatment-emergent adverse events | single dose, and twice daily continuous dosing for 21 days | Other safety and tolerability parameters including 12-lead ECG, vital signs, blood pressure/pulse, temperature, physical examination, laboratory parameters (hematology, blood biochemistry, coagulant examination, thyroid function test and urine test), and ECOG score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | single dose, and twice daily continuous dosing for 21 days | Peak Plasma Concentration |
| AUC | single dose, and twice daily continuous dosing for 21 days | Area under the plasma concentration versus time curve |
Other
| Measure | Time frame | Description |
|---|---|---|
| Explore potential predictive and prognostic biomarkers associated with telatinib treatment | prior to treatment and after 21-day treatment | Plasma level of soluble VEGFR2 |
Countries
China
Outcome results
None listed