Solid TumorPhase 1NCT02966171
A Dose Escalation Study to Assess the Safety and Tolerability of HMPL-453 in Patients With Advanced Solid Malignancies
A Phase 1 study testing HMPL-453 in people with Solid Tumor, run by Hutchison Medipharma Limited at 4 sites in Australia.
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. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- HMPL-453
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 4 sitesAustralia
- Study dates
- Jan 2017to 23 Aug 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Prior or current treatment with any selective FGFR inhibitor.
Trial locations and contacts
4 sites in 1 country.
Australia4 sites
Peninsula and Southeast Oncology
Frankston, Victoria, 3199
Monash Medical Centre
Melbourne, Victoria, 3168
St Vincent's Cancer Services
Sydney, New South Wales, 2010
Chris O'Brien Lifehouse
Sydney, New South Wales, 2050
About this study
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
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.
Read the 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.
- Conditions
- Solid Tumor
- Being tested
- HMPL-453
- Keywords
- Advanced Solid Malignancies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-453Drug
oral administration
| Study group | Role | What they receive |
|---|---|---|
| HMPL-453 | Experimental | 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. Receives: Drug: HMPL-453 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs by the NCI CTCAE v4.03
Measured: Cycle 1 (DLT assessment window, 28 days) of multiple dosing peroid
Secondary outcomes (12)
Incidence of AEs, clinically significant laboratory abnormalities, and electrocardiographic (ECG) changes and vital signs
Measured: from first dose to 30 days after last dose of study treatment
maximum plasma concentration (Cmax)
Measured: from first dose to day 56 of multiple dosing peroid
time to reach maximum concentration (Tmax)
Measured: from first dose to day 56 of multiple dosing peroid
terminal half-life (t1/2)
Measured: from first dose to day 56 of multiple dosing peroid
area under the concentration-time curve (AUC0-t)
Measured: from first dose to day 56 of multiple dosing peroid
apparent clearance (CL/F)
Measured: from first dose to day 56 of multiple dosing peroid
Serum phosphate level increases
Measured: from first dose to Day 21 of the last treatment cycle
Objective response rate (ORR)
Measured: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Duration of response (DoR)
Measured: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Disease Control Rate (DCR)
Measured: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
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.
Measured: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Progression free survival (PFS)
Measured: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2016 (estimated)
- Study startJan 2017
- Primary completion23 Aug 2018
- Study completion23 Aug 2018
Why it stopped: The study was terminated on 23AUG2018 for safety reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchison Medipharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Weiss Yang, Study director, Hutchison Medipharma Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02966171
- Sponsor's protocol ID
- 2015-453-00AU1
- Status last verified
- Nov 2018
- First submitted
- 27 Oct 2016
- Last updated
- 21 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02966171
- Acronym / sponsor ID
- 2015-453-00AU1
- Conditions
- Solid Tumor
- Keywords
- Advanced Solid Malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated on 23AUG2018 for safety reasons.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Hutchison Medipharma LimitedIndustry (pharma, biotech, devices)
- Study start
- Jan 2017 (actual)
- Primary completion
- 23 Aug 2018 (actual)
- Study completion
- 23 Aug 2018 (actual)
- First posted
- 17 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HMPL-453 | Experimental | Drug: HMPL-453Two 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. |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (1 listed)
- Prior or current treatment with any selective FGFR inhibitor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-453oral administration | Drug | HMPL-453 |
Primary outcome
Incidence of DLTs by the NCI CTCAE v4.03
Time frame: Cycle 1 (DLT assessment window, 28 days) of multiple dosing peroid
12 secondary outcomes
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
maximum plasma concentration (Cmax)
Time frame: from first dose to day 56 of multiple dosing peroid
time to reach maximum concentration (Tmax)
Time frame: 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
area under the concentration-time curve (AUC0-t)
Time frame: from first dose to day 56 of multiple dosing peroid
apparent clearance (CL/F)
Time frame: from first dose to day 56 of multiple dosing peroid
Serum phosphate level increases
Time frame: from first dose to Day 21 of the last treatment cycle
Objective response rate (ORR)
Time frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Duration of response (DoR)
Time frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Disease Control Rate (DCR)
Time frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Change in tumor size
Time frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Progression free survival (PFS)
Time frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks)
Results and safety
The study was stopped early (reason given: The study was terminated on 23AUG2018 for safety reasons.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Weiss Yang study director
Hutchison Medipharma Limited
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HMPL-453 in people with Solid Tumor, run by Hutchison Medipharma Limited at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was terminated on 23AUG2018 for safety reasons.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of DLTs by the NCI CTCAE v4.03 (time frame: Cycle 1 (DLT assessment window, 28 days) of multiple dosing peroid). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2018.