- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02966171
A Dose Escalation Study to Assess the Safety and Tolerability of HMPL-453 in Patients With Advanced Solid Malignancies
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
Study Overview
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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New South Wales
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Sydney, New South Wales, Australia, 2010
- St Vincent's Cancer Services
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Sydney, New South Wales, Australia, 2050
- Chris O'Brien Lifehouse
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Victoria
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Frankston, Victoria, Australia, 3199
- Peninsula and Southeast Oncology
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Melbourne, Victoria, Australia, 3168
- Monash Medical Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HMPL-453
Two strengths of HMPL-453 tablets (25 mg and 100 mg based on the free base) will be used for clinical studies.
The drug products are coated tablets, which are packaged in white induction sealed HDPE bottles.
HMPL-453 will be administered to patients as oral tablet(s) on a daily basis, untill disease progression, intolerable toxicity, or death.
Dose levels are to be potentially tested in this study include 25, 50, 100, 200, 300, 400, and 500 mg/day.
|
oral administration
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of DLTs by the NCI CTCAE v4.03
Time Frame: Cycle 1 (DLT assessment window, 28 days) of multiple dosing peroid
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Cycle 1 (DLT assessment window, 28 days) of multiple dosing peroid
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of AEs, clinically significant laboratory abnormalities, and electrocardiographic (ECG) changes and vital signs
Time Frame: from first dose to 30 days after last dose of study treatment
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from first dose to 30 days after last dose of study treatment
|
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maximum plasma concentration (Cmax)
Time Frame: from first dose to day 56 of multiple dosing peroid
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from first dose to day 56 of multiple dosing peroid
|
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time to reach maximum concentration (Tmax)
Time Frame: from first dose to day 56 of multiple dosing peroid
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from first dose to day 56 of multiple dosing peroid
|
|
terminal half-life (t1/2)
Time Frame: from first dose to day 56 of multiple dosing peroid
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from first dose to day 56 of multiple dosing peroid
|
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area under the concentration-time curve (AUC0-t)
Time Frame: from first dose to day 56 of multiple dosing peroid
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from first dose to day 56 of multiple dosing peroid
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apparent clearance (CL/F)
Time Frame: from first dose to day 56 of multiple dosing peroid
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from first dose to day 56 of multiple dosing peroid
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Serum phosphate level increases
Time Frame: from first dose to Day 21 of the last treatment cycle
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from first dose to Day 21 of the last treatment cycle
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Objective response rate (ORR)
Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Duration of response (DoR)
Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Disease Control Rate (DCR)
Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Change in tumor size
Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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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.
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Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Progression free survival (PFS)
Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
FGFR genetic alterations status
Time Frame: expected average of 16 weeks
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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.
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expected average of 16 weeks
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FGFR pathway inhibition by pERK
Time Frame: from first dose to Day 15 of the first treatment cycle
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Dose expansion stage (optional): explores the FGFR pathway inhibition in the fresh tumor samples pre- and after the treatment of HMPL-453.
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from first dose to Day 15 of the first treatment cycle
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Weiss Yang, Hutchison Medipharma Limited
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2015-453-00AU1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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