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

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ClinicalTrials.gov Identifier: NCT03160833
Recruitment Status : Recruiting
First Posted : May 19, 2017
Last Update Posted : November 12, 2018
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Brief 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.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: HMPL-453 Phase 1 Phase 2

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 ( 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label, Multi-center, Dose Escalation Study
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 23, 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : October 2019

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 (high-density polyethylene) bottles. HMPL-453 will be administered to patients as oral tablet(s) on a daily basis, until disease progression, intolerable toxicity, or death. Dose levels are to be potentially tested in this study include 50, 100, 200, 300, 400, and 500 mg/day
Drug: HMPL-453
oral administrative




Primary Outcome Measures :
  1. Incidence of DLTs by the NCI CTCAE v4.03 [ Time Frame: Cycle 1 (DLT assessment window 28 days) ]
    Incidence of DLTs by the NCI CTCAE v4.03


Secondary Outcome Measures :
  1. Incidence of AEs and clinically significant laboratory abnormalities [ Time Frame: From first dose to 30 days after last dose of study treatment ]
    incidence of any AEs associated to treatment

  2. maximum plasma concentration (Cmax) [ Time Frame: From first dose to day 56 of multiple dosing period ]
    maximum plasma concentration (Cmax) of HMP 453

  3. time to reach maximum concentration (Tmax) [ Time Frame: From first dose to day 56 of multiple dosing period ]
    time to reach maximum concentration (Tmax) of HMP 453

  4. terminal half-life (t1/2) [ Time Frame: From first dose to day 56 of multiple dosing period ]
    terminal half-life (t1/2) of HMP-453

  5. area under the concentration-time curve (AUC0-t) [ Time Frame: From first dose to day 56 of multiple dosing period ]
    area under the concentration-time curve (AUC0-t) of HMP453

  6. apparent clearance (CL/F) [ Time Frame: From first dose to day 56 of multiple dosing period ]
    apparent clearance (CL/F) of HMP 453

  7. Serum phosphate level increases [ Time Frame: From first dose to Day 21 of the last treatment cycle ]
    to evaluate the fluctuate level of Serum phosphate level

  8. Objective response rate (ORR) [ Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks) ]
    per RECIST

  9. Duration of response (DoR) [ Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks) ]
    from the date of response to progress or death

  10. Disease Control Rate (DCR) [ Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks) ]
    the response rate of PR (partial response) +CR(complete response) +SD (stable disease)

  11. Change in tumor size [ Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks) ]
    per RECIST to evaluate the change of target and non-target lesions

  12. Progression free survival (PFS) [ Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks) ]
    Per RECIST 1.1



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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03160833


Contacts
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Contact: Ken Chen, Master 862120673000 ext 5238 jianfengc@hmplglobal.com
Contact: Xuefeng Zhao, MD

Locations
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China, Beijing
Beijing 307 Hospital Not yet recruiting
Beijing, Beijing, China, 10000
Contact: Jianming Xu, MD         
Principal Investigator: Jianming Xu, MD         
China, Guangdong
Cancer center of SYSU Recruiting
Guangzhou, Guangdong, China, 510000
Contact: Ruihua XU, Doctor         
Principal Investigator: Ruihua Xu, Doctor         
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
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Study Director: Weiss Yang, Doctor HMPL

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Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT03160833     History of Changes
Other Study ID Numbers: 2015-453-00CH1
First Posted: May 19, 2017    Key Record Dates
Last Update Posted: November 12, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hutchison Medipharma Limited:
HMPL453
solid tumor
dose escalation