A Dose Escalation Study to Assess the Safety and Tolerability of HMPL-453 in Patients With Advanced Solid Malignancies

Solid Tumor Clinical Trial

Official title:

A Phase I, 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: Terminated

Administrative data

• NCT number: NCT02966171
• Other study ID #: 2015-453-00AU1
• Status: Terminated
• Phase: Phase 1
• Start date: January 2017
• Est. completion date: August 23, 2018

Study information

• Verified date: November 2018
• Source: Hutchison Medipharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a first-time-in-human, phase I, open-label, dose-escalation study of HMPL-453 in patients with advanced or metastatic solid malignancies who have failed or are intolerable to standard therapies or for whom no standard therapies exist. There are preliminary two stages in this study: a dose-escalation stage (stage 1) and a dose-expansion stage (stage 2). We will decide whether to conduct stage 2 or not one month after the last patient included in stage 1.

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 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 < 2 CTCAE grade 2 toxicities 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, PD profile, and preliminary anti-tumor activity of HMPL-453 at the RP2D in approximately 10 patients with advanced solid tumor. Patients with FGFR dysregulated advanced solid tumors, including but not limited to, advanced gastric cancer, advanced urothelial bladder cancer, or advanced cholangiocarcinoma (patients with cancers of the gallbladder or ampulla of Vater are not eligible) 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: Terminated
• Enrollment: 14
• Est. completion date: August 23, 2018
• Est. primary completion date: August 23, 2018
• 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 performance status of 0 or 1

Exclusion Criteria:

• Prior or current treatment with any selective FGFR inhibitor.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• HMPL-453
oral administration

Locations

Country	Name	City	State
Australia	Peninsula and Southeast Oncology	Frankston	Victoria
Australia	Monash Medical Centre	Melbourne	Victoria
Australia	Chris O'Brien Lifehouse	Sydney	New South Wales
Australia	St Vincent's Cancer Services	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	FGFR genetic alterations status	Dose Escalation stage (optional): to retrospectively determine the FGFR genetic alterations in tumor sections for the patients who have either a complete or partial response as per RECIST 1.1.	expected average of 16 weeks
Other	FGFR pathway inhibition by pERK	Dose expansion stage (optional): explores the FGFR pathway inhibition in the fresh tumor samples pre- and after the treatment of HMPL-453.	from first dose to Day 15 of the first treatment cycle
Primary	Incidence of DLTs by the NCI CTCAE v4.03		Cycle 1 (DLT assessment window, 28 days) of multiple dosing peroid
Secondary	Incidence of AEs, clinically significant laboratory abnormalities, and electrocardiographic (ECG) changes and vital signs		from first dose to 30 days after last dose of study treatment
Secondary	maximum plasma concentration (Cmax)		from first dose to day 56 of multiple dosing peroid
Secondary	time to reach maximum concentration (Tmax)		from first dose to day 56 of multiple dosing peroid
Secondary	terminal half-life (t1/2)		from first dose to day 56 of multiple dosing peroid
Secondary	area under the concentration-time curve (AUC0-t)		from first dose to day 56 of multiple dosing peroid
Secondary	apparent clearance (CL/F)		from first dose to day 56 of multiple dosing peroid
Secondary	Serum phosphate level increases		from first dose to Day 21 of the last treatment cycle
Secondary	Objective response rate (ORR)		Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary	Duration of response (DoR)		Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary	Disease Control Rate (DCR)		Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary	Change in tumor size	Tumor size is defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions (TLs). Percentage change in tumor size will be determined for patients with measurable disease at baseline and is derived at each visit by the percentage change in the sum of the diameters of TLs compared to baseline.	Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary	Progression free survival (PFS)		Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)