Clinical trial NCT04290325: HMPL-453 in Advanced Malignant Mesothelioma
Official title: A Phase II, Single Arm, Multicenter and Open Labelstudy Evaluating the Efficacy, Safety and Pharmacokinetics of HMPL-453 in Patient With Advanced Malignant Mesothelioma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced Malignant Mesothelioma
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2020-02-28
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 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
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: 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
measure: 12 weeks DCR
timeFrame: measured on 12 weeks
measure: Time to Response (TTR)
timeFrame: measured on 4 weeks
measure: Duration of response (DoR)
timeFrame: measured on 30 weeks
measure: 12 weeks PFS
timeFrame: measured on 12 weeks
measure: Progression free survival (PFS)
timeFrame: measured on 20 weeks
measure: Overall survival (OS)
timeFrame: measured on 60weeks
measure: Adverse Event (AE) of HMPL-453 monitoring
timeFrame: Measured from the first dose to within 30 days after the end of treatment.
measure: Maximum plasma concentration (Cmax) of HMPL-453
timeFrame: measured on Cycle 1 day 15 and day 16
measure: The time to Cmax (Tmax) of HMPL-453
timeFrame: measured on Cycle 1 day 15 and day 16
measure: The area under the plasma concentration-time curve (AUC) of HMPL-453
timeFrame: measured on Cycle 1 day 15 and day 16
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
Study officials:
affiliation: Shanghai Chest Hospital
name: Shun Lu, Prof.
role: PRINCIPAL_INVESTIGATOR
References: