Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03160833
Recruitment Status : Active, not recruiting
First Posted : May 19, 2017
Last Update Posted : February 13, 2020
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Tracking Information
First Submitted Date  ICMJE May 17, 2017
First Posted Date  ICMJE May 19, 2017
Last Update Posted Date February 13, 2020
Actual Study Start Date  ICMJE May 23, 2017
Actual Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2017)
  • 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
  • maximum plasma concentration (Cmax) [ Time Frame: From first dose to day 56 of multiple dosing period ]
    maximum plasma concentration (Cmax) of HMP 453
  • 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
  • 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
  • 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
  • apparent clearance (CL/F) [ Time Frame: From first dose to day 56 of multiple dosing period ]
    apparent clearance (CL/F) of HMP 453
  • 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
  • Objective response rate (ORR) [ Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks) ]
    per RECIST
  • 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
  • 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)
  • 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
  • Progression free survival (PFS) [ Time Frame: Every 8 weeks while being treated with HMPL-453 (expected average of 16 weeks) ]
    Per RECIST 1.1
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of HMPL-453 in Patients With Advanced Solid Malignancies
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label, Multi-center, Dose Escalation Study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor, Adult
Intervention  ICMJE Drug: HMPL-453
oral administrative
Study Arms  ICMJE 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
Intervention: Drug: HMPL-453
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 12, 2020)
33
Original Estimated Enrollment  ICMJE
 (submitted: May 18, 2017)
96
Estimated Study Completion Date  ICMJE June 30, 2020
Actual Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03160833
Other Study ID Numbers  ICMJE 2015-453-00CH1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Hutchison Medipharma Limited
Study Sponsor  ICMJE Hutchison Medipharma Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Weiss Yang, Doctor HMPL
PRS Account Hutchison Medipharma Limited
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP