Advanced Malignant Mesothelioma
Conditions
Brief summary
This is a phase II, single arm, multicenter and open-label study to evaluate the efficacy, safety and pharmacokinetic of HMPL-453 in patient with advanced Malignant Mesothelioma
Detailed description
Histologically confirmed patients with advanced malignant mesothelioma that who was failure of the first -line systemic therapy
Interventions
DRUGHMPL-453
HMPL-453 tablet
Sponsors
Hutchison Medipharma Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1.Signed written informed consent; * 2.18 years of age or older; * 3.Histologically diagnosed malignant mesothelioma (including pleura, peritoneum, pericardium, and testicular tendon sheath origin, cell type epithelioid, sarcoma-like, or mixed type), and cannot be cured radically; * 4.Received one to three regimen of prior systemic therapy and then experienced documented radiographic progression or intolerable toxicity; * 5.Patients agreed to provide tumor tissue for FGF/FGFR testing; * 6.Measurable disease by RECIST version 1.1 criteria; * 7.ECOG performance status ≤ 2.;
Exclusion criteria
* 1.Previous treatment with any FGFR inhibitor; * 2.Received systemic anti-cancer therapy within 3 weeks of the first dose of HMPL-453; * 3.Major surgery within 4 weeks of the first dose of HMPL-453; * 4.Use of a strong inducer or inhibitor of cytochrome P450 3A4 (CYP3A4) within 1 week of the first dose of HMPL-453; * 5.Inadequate conditions as indicated by the following laboratory values: * Absolute neutrophil count (ANC)\<1.5 x 109/L * Hemoglobin \< 80 g/L * Platelet count \<80 x 109/L * 6.Any of the following conditions of liver and kidney insufficiency: * Total bilirubin \> 1.5 x ULN * AST and ALT \> 2.5 x ULN (\> 5 x ULN for patients with liver metastases) * Creatinine clearance of \< 50 mL/min as estimated by the Cockcroft-Gault equation * 7.International normalized ratio (INR) \>1.5 or activated partial thromboplastin time (aPTT) \>1.5 x ULN; * 8.Clinical significant liver disease; * 9.Known human immunodeficiency virus (HIV) infection * 10.Previous history of retinal detachment; * 11.Unable to swallow the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | measured up to 6 months after the last subject has been enrolled or all subjects have finished their last PFS follow up, whichever comes first | Evaluating ORR of HMPL-453 in patient with advanced malignant mesothelioma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | measured up to 6 months after the last subject has been enrolled or all subjects have finished their last PFS follow up, whichever comes first | Evaluating DCR of HMPL-453 in patient with advanced malignant mesothelioma |
| 12 weeks DCR | measured on 12 weeks | Evaluating 12 weeks DCR of HMPL-453 in patient with advanced malignant mesothelioma |
| Time to Response (TTR) | measured on 4 weeks | Evaluating TTR of HMPL-453 in patient who achieved partial response or complete response according to RECIST 1.1 or mRECIST 1.1 |
| Duration of response (DoR) | measured on 30 weeks | Evaluating DoR of HMPL-453 in patient from subject first achieve a complete remission, or partial remission to patient PD, or death whichever comes first. |
| 12 weeks PFS | measured on 12 weeks | Evaluating 12 weeks PFS rate of HMPL-453 in patient with advanced malignant mesothelioma |
| Progression free survival (PFS) | measured on 20 weeks | Evaluating PFS of HMPL-453 in patient with advanced malignant mesothelioma. |
| Overall survival (OS) | measured on 60weeks | Evaluating OS of HMPL-453 in patient with advanced malignant mesothelioma |
| Adverse Event (AE) of HMPL-453 monitoring | Measured from the first dose to within 30 days after the end of treatment. | The safety endpoints include adverse events (AEs) and serious adverse events (SAEs). Reporting of safety, extent of exposure, concomitant medications and discontinuation of study therapy will be based on all subjects who received at least 1 dose of treatment. The adverse events will be registered according to NCI CTCAE 5.0. |
| Maximum plasma concentration (Cmax) of HMPL-453 | measured on Cycle 1 day 15 and day 16 | Evaluating Cmax of Continuous dosing of HMPL-453 in patient with advanced malignant |
| The time to Cmax (Tmax) of HMPL-453 | measured on Cycle 1 day 15 and day 16 | Evaluating Tmax of Continuous dosing of HMPL-453 in patient with advanced malignant |
| The area under the plasma concentration-time curve (AUC) of HMPL-453 | measured on Cycle 1 day 15 and day 16 | Evaluating AUC from 0 to the time of the last measurable concentration of HMPL-453 in patient with advanced malignant |
Countries
China
Contacts
Primary ContactWenjuan Ding
Backup ContactChen Yu
Outcome results
None listed