Back to resultsStudy of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas
Primary Purpose
Glioma
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
PLB1001
Sponsored by
About this trial
This is an interventional treatment trial for Glioma
Eligibility 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
Sites / Locations
- Beijing Shijitan Hospital,CMU
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PLB1001
Arm Description
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.
Outcomes
Primary Outcome Measures
Percentage of participants with dose-limiting toxicities
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
Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite
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
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
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
Preliminary antitumor activity of PLB1001 assessed using RANO
Full Information
NCT ID
NCT02978261
First Posted
November 28, 2016
Last Updated
March 2, 2020
Sponsor
Beijing Pearl Biotechnology Limited Liability Company
1. Study Identification
Unique Protocol Identification Number
NCT02978261
Brief Title
Study of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas
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 Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
April 2018 (Actual)
Study Completion Date
December 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Pearl Biotechnology Limited Liability Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PLB1001
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
PLB1001
Other Intervention Name(s)
Bozitinib
Intervention Description
PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.
Primary Outcome Measure Information:
Title
Percentage of participants with dose-limiting toxicities
Description
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).
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite
Description
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 Frame
Day 1-3 Single Dose and Day 1-28 Steady State
Title
Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite
Description
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 Frame
Day 1-3 Single Dose and Day 1-28 Steady State
Title
Time to Cmax (Tmax) of PLB1001 and its metabolite
Description
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 Frame
Day 1-3 Single Dose and Day 1-28 Steady State
Title
Preliminary antitumor activity of PLB1001
Description
Preliminary antitumor activity of PLB1001 assessed using RANO
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenbin Li, MD
Organizational Affiliation
Beijing Shijitan Hospital, CMU
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Shijitan Hospital,CMU
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100038
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
30343896
Citation
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.
Results Reference
derived
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Study of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas
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