A Dose Escalation Study to Assess the Safety and Tolerability of HMPL-453 in Patients With Advanced Solid Malignancies

NCT02966171 | Terminated Phase 1 DMC

• 1 other identifier: 2015-453-00AU1
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

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.

Conditions

Solid Tumor

Keywords

Advanced Solid Malignancies

Outcome Measures

Primary Outcomes (1)

• Incidence of DLTs by the NCI CTCAE v4.03

  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

  from first dose to 30 days after last dose of study treatment

• maximum plasma concentration (Cmax)

  from first dose to day 56 of multiple dosing peroid

• time to reach maximum concentration (Tmax)

  from first dose to day 56 of multiple dosing peroid

• terminal half-life (t1/2)

  from first dose to day 56 of multiple dosing peroid

• area under the concentration-time curve (AUC0-t)

  from first dose to day 56 of multiple dosing peroid

Other Outcomes (2)

• FGFR genetic alterations status

  expected average of 16 weeks

• FGFR pathway inhibition by pERK

  from first dose to Day 15 of the first treatment cycle

Study Arms (1)

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.

Drug: HMPL-453

Interventions

HMPL-453 DRUG

oral administration

HMPL-453

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Prior or current treatment with any selective FGFR inhibitor.

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (4)

St Vincent's Cancer Services

Sydney, New South Wales, 2010, Australia

Location

Chris O'Brien Lifehouse

Sydney, New South Wales, 2050, Australia

Location

Peninsula and Southeast Oncology

Frankston, Victoria, 3199, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

Study Officials

• Weiss Yang

  Hutchison Medipharma Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: November 17, 2016
• Study Start: January 1, 2017
• Primary Completion: August 23, 2018
• Study Completion: August 23, 2018
• Last Updated: November 21, 2018

Record last verified: 2018-11

Locations

AU (4)