A Study of HMPL-453 in Patients With Advanced Solid Malignancies

Solid Tumor, Adult Clinical Trial

Official title:

A Phase I/II, Open-label, Multi-center, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of HMPL-453 in Patients With Advanced Solid Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03160833
• Other study ID #: 2015-453-00CH1
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 23, 2017
• Est. completion date: June 30, 2020

Study information

• Verified date: February 2020
• Source: Hutchison Medipharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a dose escalation study consisting of two stages: Dose-escalation stage (stage 1): Patients will take a single dose of HMPL-453 on Day 1 and will be followed for one week for safety observations. After one week of observation, if no safety issues occur, patients can continue multiple dosing of HMPL-453 QD (quaque die) and start on the DLT (Dose Limited Toxicity) assessment cycles. Each cycle consists of 28-days. Patients are required to draw blood samples for PK and safety analysis at specific time points during the treatment; Dose-Expansion Stage (Stage 2): This stage is to further evaluate the safety, tolerability, PD (pharmacodynamics) profile, and preliminary anti-tumor activity of HMPL-453 at the RP2D (recommended phase 2 dose) in approximately 10 patients with advanced solid tumor.

Description:

Dose-escalation stage (stage 1): Patients participating in the dose-escalation stage will take a single dose of HMPL-453 on Day 1 and will be followed for one week for safety observations. After one week of observation, if no safety issues occur, patients can continue multiple dosing of HMPL-453 QD and start on the DLT assessment cycles. Each cycle consists of 28-days. Patients are required to draw blood samples for PK and safety analysis at specific time points during the treatment.

The 3+3 design will be employed for the dose escalation and MTD ( maximum tolerated dose) determination. To limit the number of patients being exposed to potentially ineffective doses, one patient will be enrolled and dosed in the initial dose cohort. If there are no DLT or less than grade 2 toxicities of Common Terminology Criteria for Adverse Event ( CTC AE ) occur in the first treatment cycle, then the study will be escalated to the next dose cohort. Otherwise, the trial will revert to a standard 3+3 design.

Dose-Expansion Stage (Stage 2): This stage is to further evaluate the safety, tolerability, pharmacokinetics (PK) profile, and preliminary anti-tumor activity of HMPL-453 at the RP2D in approximately 60 patients with advanced solid tumor. Patients with FGFR ( Fibroblast Growth Factor Receptor) dysregulated advanced solid tumors, including but not limited to advanced urothelial bladder cancer, advanced cholangiocarcinoma (patients with cancers of the gallbladder or ampulla of Vater are not eligible) and others solid tumors are preferred to be enrolled.

Expansion stage will begin after dose-escalation stage is completed and the MTD/RP2D has been determined. Patients will receive HMPL-453 with 28-day treatment cycles until disease progression, death, intolerable toxicity, no longer benefiting from the study treatment per investigator's discretion, or withdrawal of consent, whichever comes first.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 33
• Est. completion date: June 30, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

Inclusion Criteria:

• In the dose escalation stage, patients with locally advanced, or metastatic solid tumor who have failed, or intolerable to, standard therapies or for whom no standard therapies exist will be enrolled.

• In the dose expansion stage, patients with locally advanced, or metastatic solid tumor and FGFR dysregulation who have failed or intolerable to standard therapies or no standard therapies exist are to be enrolled.

• In the dose escalation stage: evaluable or measurable disease according to RECIST Version 1.1. In the dose expansion stage: measurable disease according to RECIST Version 1.1.

• Life expectancy of at least 12 weeks.

• ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.

Exclusion Criteria:

• Prior or current treatment with any selective FGFR inhibitor.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Drug:
• HMPL-453
oral administrative

Locations

Country	Name	City	State
China	Beijing 307 Hospital	Beijing	Beijing
China	Cancer center of SYSU	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of DLTs by the NCI CTCAE v4.03	Incidence of DLTs by the NCI CTCAE v4.03	Cycle 1 (DLT assessment window 28 days)
Secondary	Incidence of AEs and clinically significant laboratory abnormalities	incidence of any AEs associated to treatment	From first dose to 30 days after last dose of study treatment
Secondary	maximum plasma concentration (Cmax)	maximum plasma concentration (Cmax) of HMP 453	From first dose to day 56 of multiple dosing period
Secondary	time to reach maximum concentration (Tmax)	time to reach maximum concentration (Tmax) of HMP 453	From first dose to day 56 of multiple dosing period
Secondary	terminal half-life (t1/2)	terminal half-life (t1/2) of HMP-453	From first dose to day 56 of multiple dosing period
Secondary	area under the concentration-time curve (AUC0-t)	area under the concentration-time curve (AUC0-t) of HMP453	From first dose to day 56 of multiple dosing period
Secondary	apparent clearance (CL/F)	apparent clearance (CL/F) of HMP 453	From first dose to day 56 of multiple dosing period
Secondary	Serum phosphate level increases	to evaluate the fluctuate level of Serum phosphate level	From first dose to Day 21 of the last treatment cycle
Secondary	Objective response rate (ORR)	per RECIST	Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary	Duration of response (DoR)	from the date of response to progress or death	Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary	Disease Control Rate (DCR)	the response rate of PR (partial response) +CR(complete response) +SD (stable disease)	Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary	Change in tumor size	per RECIST to evaluate the change of target and non-target lesions	Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary	Progression free survival (PFS)	Per RECIST 1.1	Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)