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To investigate tolerability, safety, pharmacokinetics and efficacy of C-met Kinase Inhibitor HS-10241 single agent or combined with Apatinib in Subjects With Advanced Solid Tumours that are not eligible for conventional or intensive treatment. The dose of HS-10241 will be escalated to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of HS-10241 single agent and in combination with Apatinib in advanced cancer patients. At the same time, pharmacokinetic characteristics and preliminary efficacy of HS-10241 or combined with Apatinb will be observed in advanced cancer patients. To determine the recommended dosage regimen for phase II.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HS-1024+apatinib | Experimental | For part 1 (PK study) subjects will be given single dose of HS-10241 and then multiple dose of HS-10241 (1 cycle, each cycle 14days) and then HS-10241+aptatinib (each cycle 21 days) until PD. For part 2 (expansion study) subjects will be given HS-10241+aptatinib (each cycle 21 days) until PD (Progression of disease). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HS-10241 | Drug | HS-10241 is provided as white, film-coated,immediate release tablets containing HS-10241 at dosage strengths of 20mg/50mg/100 mg. Multiple tablets of HS-10241 will be administered daily to achieve targeted doses of HS-10241: 200 mg-1200 mg. Tablets will be orally administered with 240 ml water, once daily, 1 hour before/after a meal. |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicities (DLT) | To assess MTD and DLT of HS-10241 single agent(D1-D17) then combined with aptatinib (D18-D38) in patients with advanced solid tumors.According to the "3+3" dose escalation design DLT will be determined. | Day1 to day 38 (DLT observation period) |
| Maximum Tolerated Dose (MTD) | One dose level below the dose level determined as DLT will be MTD. | Day1 to day 38 (DLT observation period) |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events and Serious Adverse Events | To asess the safety of HS-10241 single agent the combined with apatinib in patients with advanced solid tumor. | From the day of ICF (Informed Consent Form) until 30 days after the last dose |
| The measurement of maximum plasma concentration (Cmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yi Li, Ph.D | Contact | 021-68868570 | liuy@shhrp.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| West China Hospital, Sichuan University | Recruiting | Chendu | China |
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| Apatinib | Drug | Apatinib is provided as white, film-coated,immediate release tablets containing aptinib at dosage strengths of 250mg. Apatinib will be administered daily to achieve targeted doses of 500 mg. Tablets will be orally administered with 240 ml water, once daily, 1 hour before/after a meal. |
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Including HS-10241 single dose (D1)/multiple dose of HS-10241(D17) and multiple dose of Apatinib(D38). |
| Day 1 to day 38 |
| The measurement of the area under the plasma concentration-time versus time curve(AUC) | Area Under Curve(AUC0-t) will be measured after single dose administration of HS-10241 at day 1.AUC0-t and AUC0-inf are measured after repeated once-daily dose administration of HS-10241 at day 14.AUC0-t and AUC0-inf are measured after repeat once-daily dose administration of apatinib at day 38. | Day 1 to day 38 |
| The measurement of the area under the plasma concentration-time versus time curve(AUC) | AUC(0-inf) will be measured after single dose administration of HS-10241 at day 1.AUC0-t and AUC0-inf are measured after repeated once-daily dose administration of HS-10241 at day 14.AUC0-t and AUC0-inf are measured after repeat once-daily dose administration of apatinib at day 38. | Day 1 to day 38 |
| The measurement of time of maximum plasma concentration (Tmax) | Including HS-10241 single dose (D1)/multiple dose of HS-10241(D17) and multiple dose of apatinib(D38). | Day 1 to day 38 |
| The measurement of elimination half life (T1/2) | T1/2 is measured after single dose administration of HS-10241 at day 1. T1/2 is measured after repeat once-daily dose administration of HS-10241 at day 17. | Day 1 to day 38 |
| The Measurement of mean retention time (MRT) | MRT is measured after single dose administration of HS-10241 at day 1. | Day 1 to day 38 |
| The measurement of apparent volume of distribution (Vd) | Vd is measured after single dose administration of HS-10241 at day 1. Vd is measured after repeated once-daily dose administration of HS-10241 at day 17. | Day 1 to day 38 |
| The measurement of clearance (Cl) | Vd is measured after single dose administration of HS-10241 at day 1. Vd is measured after repeated once-daily dose administration of HS-10241 at day 17. | Day 1 to day 38 |
| Duration of Response Rate | Determined using RECIST v1.1 criteria | Approximately 1 year |
| Progression-Free Survival | Determined using RECIST v1.1 criteria | Approximately 1 year |
| Objective Response Rate | Determined using RECIST v1.1 criteria | Approximately 1 year |
| ID | Term |
|---|---|
| C553458 | apatinib |
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