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Study of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas

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: NCT02978261
Recruitment Status : Completed
First Posted : November 30, 2016
Last Update Posted : March 4, 2020
Sponsor:
Information provided by (Responsible Party):
Beijing Pearl Biotechnology Limited Liability Company

Tracking Information
First Submitted Date  ICMJE November 28, 2016
First Posted Date  ICMJE November 30, 2016
Last Update Posted Date March 4, 2020
Actual Study Start Date  ICMJE September 2016
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2016)
Percentage of participants with dose-limiting toxicities [ Time Frame: 2 years ]
The primary endpoint is evaluation of safety and tolerability during all the study of therapy following the initiation of single and multiple doses of PLB1001. The safety and tolerability variables to be evaluated in this study are adverse events, vital signs, and electrocardiograms (ECGs), Incidence and nature of DLTs (Dose-Limiting Toxicities), to determine the MTD (Maximum Tolerated Dose).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2016)
  • Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite [ Time Frame: Day 1-3 Single Dose and Day 1-28 Steady State ]
    In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy
  • Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite [ Time Frame: Day 1-3 Single Dose and Day 1-28 Steady State ]
    In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy
  • Time to Cmax (Tmax) of PLB1001 and its metabolite [ Time Frame: Day 1-3 Single Dose and Day 1-28 Steady State ]
    In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy
  • Preliminary antitumor activity of PLB1001 [ Time Frame: 2 years ]
    Preliminary antitumor activity of PLB1001 assessed using RANO
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 Study of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas
Official Title  ICMJE A Phase I, Open-label, Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas
Brief Summary This phase I, open-label, dose-escalation study was conducted to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), dose-limiting toxicities (DLTs), pharmacokinetics (PK) profile, and preliminary antitumor activity of single and multiple doses of PLB1001 in Patients with PTPRZ1-MET fusion gene positive recurrent high-grade Gliomas.
Detailed Description

This is a Phase I, open-label study of PLB1001 administered orally to patients with PTPRZ1-MET fusion gene positive recurrent high-grade Gliomas. The aim of dose-escalation study is to estimate the MTD and to identify the dose-limiting toxicity(DLT) and the recommended phase II dose (RP2D) for PLB1001 single agent as well as to determine the PK/PD profile. Aprox. 20 patients will be enrolled in this study.

PLB1001 is a potent selective c-Met inhibitor. PLB1001 acts on cancer by blocking abnormal cMET-mediated signaling (including PTPRZ1-MET fusion gene), leading to profound tumor growth inhibition in xenografts of PTPRZ1-MET fusion gene positive glioblastoma tumor.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioma
Intervention  ICMJE Drug: PLB1001
PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.
Other Name: Bozitinib
Study Arms  ICMJE Experimental: PLB1001
There are 4 dose cohorts, including 50mg BID,100mg BID, 200mg BID and 300mg BID in the dose escalation stage and PLB1001 will be administered orally to patients twice daily for each dose cohort.
Intervention: Drug: PLB1001
Publications * Hu H, Mu Q, Bao Z, Chen Y, Liu Y, Chen J, Wang K, Wang Z, Nam Y, Jiang B, Sa JK, Cho HJ, Her NG, Zhang C, Zhao Z, Zhang Y, Zeng F, Wu F, Kang X, Liu Y, Qian Z, Wang Z, Huang R, Wang Q, Zhang W, Qiu X, Li W, Nam DH, Fan X, Wang J, Jiang T. Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor. Cell. 2018 Nov 29;175(6):1665-1678.e18. doi: 10.1016/j.cell.2018.09.038. Epub 2018 Oct 18.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: March 2, 2020)
18
Original Estimated Enrollment  ICMJE
 (submitted: November 29, 2016)
20
Actual Study Completion Date  ICMJE December 2018
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed Informed Consent Form
  • Age≥18 years
  • Histologically or cytologically confirmed recurrent high-grade glioma after concurrent or adjuvant chemoradiotherapy
  • Prior treatment with temozolomide
  • Must have evidence of PTPRZ1-MET fusion gene positivity from the results of molecular pre-screening evaluations
  • At least one measurable lesion as per RANO
  • No evidence of recent haemorrhage on baseline MRI of the brain
  • Stable or decreasing dose of corticosteroids within 5 days prior to the first dose
  • Major surgery within 4 weeks prior to first dose of PLB1001
  • Previous anti-cancer and investigational agents within 4 weeks before first dose of PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 6 weeks before first dose of PLB1001
  • Pregnant or nursing women
  • Involved in other clinical trials <30 days prior to first dose
  • Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field
  • Karnofsky performance status ≥ 50%

Exclusion Criteria:

  • Previous or current treatment with a c-Met inhibitor or HGF-targeting therapy
  • The subject is unable to undergo MRI scan (e.g. has pacemaker)
  • Clinically significant, uncontrolled heart diseases: Unstable angina; History of documented congestive heart failure (New York Heart Association functional classification> II); Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 145 mm Hg and/or Diastolic Blood Pressure (DBP) ≥85 mm Hg; Arrhythmias.
  • Active peptic ulcer disease or gastritis
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1, except for alopecia
  • Major surgery within 4 weeks prior to first dose of PLB1001
  • Previous anti-cancer and investigational agents within 4 weeks before first dose of PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 6 weeks before first dose of PLB1001
  • Pregnant or nursing women
  • Involved in other clinical trials <30 days prior to first dose
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 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 NCT02978261
Other Study ID Numbers  ICMJE HMO-PLB1001-I-GBM-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Beijing Pearl Biotechnology Limited Liability Company
Study Sponsor  ICMJE Beijing Pearl Biotechnology Limited Liability Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wenbin Li, MD Beijing Shijitan Hospital, CMU
PRS Account Beijing Pearl Biotechnology Limited Liability Company
Verification Date August 2018

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