Phase I Study of the Volitinib (HMPL-504) in Patients With Advanced Solid Tumors (HMPL-504)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of HMPL-504 in Patients With Advanced Solid Tumors|
- The safety and tolerability of single and multiple doses of HMPL-504 administered to patients. [ Time Frame: up to 20 months ] [ Designated as safety issue: Yes ]The primary endpoint is evaluation of safety and tolerability during all the study of therapy following the initiation of multiple dosing of HMPL-504. The safety and tolerability variables to be evaluated in this study are adverse events, physical examinations, vital signs (specifically including blood pressure), clinical laboratory evaluations including serum chemistry, hematology(Maximum Tolerated Dose) , and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for protein), and electrocardiograms (ECGs) in triplicate,Incidence and nature of DLTs(Dose-Limiting Toxicity),To determine the MTD (Maximum Tolerated Dose).
- Pharmacokinetic Assessments for area under curve (AUC), Cmax and Tmax . [ Time Frame: Day 1-3 Single Dose and Day 1-21 Steady State ] [ Designated as safety issue: Yes ]In the study of single-dose, full Pharmacokinetics(PK) profiles of HMPL-504 will be obtained following administration of a single oral dose of HMPL-504 on Day 1 to Day 3. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5,2,4,6,8 hour time points on days 1,15,21of dosing in the first 21-Day cycle of therapy, and pre-dose on days 2,8,16,and 22 of the first 21-Day cycle of therapy
- Objective Response Rate （ORR) [ Time Frame: participants will be followed for the duration of hospital stay,an expected average of 3 months. ] [ Designated as safety issue: Yes ]Anti-tumoral efficacy will be assessed by best radiographic response based on Response Evaluation Criteria in Solid Tumors at baseline (Day -14 to -1) and at the end of two 21-Day cycles of therapy . For patients that continue on repeat 21-Day cycles after the primary evaluation period, progression will be assessed after each one 21-Day cycles of therapy
|Study Start Date:||February 2012|
|Study Completion Date:||May 2016|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
There are six dose cohorts,including 100, 200, 400, 600,800 and 1000 mg/day, HMPL-504 will be administered orally to patients once daily for each dose cohort.
An alternative dosing schedule of twice every day (BID) may be investigated if pharmacokinetic studies indicate faster than anticipated clearance of Volitinib(HMPL-504).
Volitinib(HMPL-504) is a tablet in the form of 25 mg ,100mgand 200 mg,oral,once daily.
Other Name: HMPL-504
This is a Phase I, first-in-human, open-label, dose-escalation study of Volitinib (HMPL-504) administered orally once every day(QD) to patients with locally advanced or metastatic solid tumors.There are two stages to this study : a dose-escalation stage and a dose-expansion stage. The dose-escalation stage is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and repeat doses of HMPL-504 given once every day (QD). An alternative dosing schedule of twice every day (BID) may be investigated if pharmacokinetic studies indicate faster than anticipated clearance of HMPL-504.
All patients will be carefully followed for adverse events during the study treatment and for 30 days after the last dose of study drug. Subjects of this study will be permitted to continue therapy with only safety monitoring and bimonthly assessments for progression, if the product is well tolerated and the subject has stable disease or better.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01773018
|Australia, Western Australia|
|Sir Charles Gairdner Hospital|
|Nedlands, Western Australia, Australia, 6009|
|Southern Health and Monash Institute of Medical Research|
|Clayton, Australia, 3168|
|Melbourne, Australia, 3084|
|Principal Investigator:||Michael Millward, MD,Ph.D||Sir Charles Gairdner Hospital & University of WA|
|Principal Investigator:||Hui Gan, MD,Ph.D||Austin Hospital, Melbourne Australia|
|Principal Investigator:||Jason Lickliter, MD,Ph.D||Southern Health and Monash Institute of Medical Research|