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Trial record 2 of 3 for:    Beijing Pearl Biotechnology

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

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ClinicalTrials.gov Identifier: NCT02978261
Recruitment Status : Recruiting
First Posted : November 30, 2016
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
Beijing Pearl Biotechnology Limited Liability Company

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.

Condition or disease Intervention/treatment Phase
Glioma Drug: PLB1001 Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: PLB1001
PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.
Other Name: Bozitinib




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Preliminary antitumor activity of PLB1001 [ Time Frame: 2 years ]
    Preliminary antitumor activity of PLB1001 assessed using RANO



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT02978261


Contacts
Contact: Weizhe Xue, Ph.D +86-10-64392756 xueweizhe@pearlbio.cn

Locations
China, Beijing
Beijing Shijitan Hospital,CMU Recruiting
Beijing, Beijing, China, 100038
Contact: Xun Kang, Master    +86-10-63926527    414569017@qq.com   
Principal Investigator: Wenbin Li, MD         
Sub-Investigator: Xun Kang, Master         
Sponsors and Collaborators
Beijing Pearl Biotechnology Limited Liability Company
Investigators
Principal Investigator: Wenbin Li, MD Beijing Shijitan Hospital, CMU

Responsible Party: Beijing Pearl Biotechnology Limited Liability Company
ClinicalTrials.gov Identifier: NCT02978261     History of Changes
Other Study ID Numbers: HMO-PLB1001-I-GBM-01
First Posted: November 30, 2016    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue