We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02966171




Registration number
NCT02966171
Ethics application status
Date submitted
27/10/2016
Date registered
17/11/2016
Date last updated
21/11/2018

Titles & IDs
Public title
A Dose Escalation Study to Assess the Safety and Tolerability of HMPL-453 in Patients With Advanced Solid Malignancies
Scientific 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
Secondary ID [1] 0 0
2015-453-00AU1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HMPL-453

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.


Treatment: Drugs: HMPL-453
oral administration

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of DLTs by the NCI CTCAE v4.03
Timepoint [1] 0 0
Cycle 1 (DLT assessment window, 28 days) of multiple dosing peroid
Secondary outcome [1] 0 0
Incidence of AEs, clinically significant laboratory abnormalities, and electrocardiographic (ECG) changes and vital signs
Timepoint [1] 0 0
from first dose to 30 days after last dose of study treatment
Secondary outcome [2] 0 0
maximum plasma concentration (Cmax)
Timepoint [2] 0 0
from first dose to day 56 of multiple dosing peroid
Secondary outcome [3] 0 0
time to reach maximum concentration (Tmax)
Timepoint [3] 0 0
from first dose to day 56 of multiple dosing peroid
Secondary outcome [4] 0 0
terminal half-life (t1/2)
Timepoint [4] 0 0
from first dose to day 56 of multiple dosing peroid
Secondary outcome [5] 0 0
area under the concentration-time curve (AUC0-t)
Timepoint [5] 0 0
from first dose to day 56 of multiple dosing peroid
Secondary outcome [6] 0 0
apparent clearance (CL/F)
Timepoint [6] 0 0
from first dose to day 56 of multiple dosing peroid
Secondary outcome [7] 0 0
Serum phosphate level increases
Timepoint [7] 0 0
from first dose to Day 21 of the last treatment cycle
Secondary outcome [8] 0 0
Objective response rate (ORR)
Timepoint [8] 0 0
Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary outcome [9] 0 0
Duration of response (DoR)
Timepoint [9] 0 0
Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary outcome [10] 0 0
Disease Control Rate (DCR)
Timepoint [10] 0 0
Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Secondary outcome [12] 0 0
Progression free survival (PFS)
Timepoint [12] 0 0
Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)

Eligibility
Key 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
Minimum age
25 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior or current treatment with any selective FGFR inhibitor.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincent's Cancer Services - Sydney
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [3] 0 0
Peninsula and Southeast Oncology - Frankston
Recruitment hospital [4] 0 0
Monash Medical Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
3168 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hutchison Medipharma Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT02966171
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Weiss Yang
Address 0 0
Hutchison Medipharma Limited
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02966171